Diagenode

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117 publications found.

Interferon-gamma rescues FK506 dampened dendritic cell calcineurin-dependent responses to Aspergillus fumigatus via Stat3 to Stat1 switching
Published: December, 2024

Abstract: IScience Highlights Calcineurin inhibitors block DC maturation in response to A. fumigatus Lack of DC maturation impairs Th1 polarization in response to A. fumigatus Interferon-γ restores maturation, pr...
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Prediction of brain metastasis development with DNA methylation signatures
Published: October, 2024

Abstract: Brain metastases (BMs) are the most common and among the deadliest brain tumors. Currently, there are no reliable predictors of BM development from primary cancer, which limits early intervention. Lung adenocarcinoma (LUAD) is the most common BM s...
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HNF1β bookmarking involves Topoisomerase 1 activation and DNA topology relaxation in mitotic chromatin
Published: October, 2024

Abstract: Highlights HNF1β mitotic site binding is preserved with a specific methanol/formaldehyde ChIP BTBD2, an HNF1β partner, mediates mitosis-specific interaction with TOP1 HNF1β recruits TOP1 and induces DNA ...
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Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma
Published: June, 2024

Abstract: Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its ...
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Detecting small cell transformation in patients with advanced EGFR mutant lung adenocarcinoma through epigenomic cfDNA profiling
Published: June, 2024

Abstract: Purpose: Histologic transformation to small cell lung cancer (SCLC) is a mechanism of treatment resistance in patients with advanced oncogene-driven lung adenocarcinoma (LUAD) that currently requires histologic review for diagnosis. Herein, we sou...
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Prostate cancer detection through unbiased capture of methylated cell-free DNA
Published: June, 2024

Abstract: Prostate cancer screening using prostate-specific antigen (PSA) has been shown to reduce mortality but with substantial overdiagnosis, leading to unnecessary biopsies. The identification of a highly specific biomarker using liquid biopsies, repres...
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The ETO2 transcriptional cofactor maintains acute leukemia by driving a MYB/EP300-dependent stemness program
Published: June, 2024

Abstract: Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized the ETO2 regulome by integrating transcriptomic and chromatin binding analyses in human erythroleukemia xenografts and controlled ETO2 de...
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Focal cortical dysplasia type II-dependent maladaptive myelination in the human frontal lobe
Published: March, 2024

Abstract: Focal cortical dysplasias (FCDs) are local malformations of the human neocortex and a leading cause of intractable epilepsy. FCDs are classified into different subtypes including FCD IIa and IIb, characterized by a blurred gray-white matter bounda...
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In vitro production of cat-restricted Toxoplasma pre-sexual stages
Published: December, 2023

Abstract: Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during i...
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Cerebrospinal fluid methylome-based liquid biopsies for accuratemalignant brain neoplasm classification.
Published: August, 2023

Abstract: BACKGROUND: Resolving the differential diagnosis between brain metastases (BM), glioblastomas (GBM), and central nervous system lymphomas (CNSL) is an important dilemma for the clinical management of the main three intra-axial brain tumor types. C...
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Differentiation block in acute myeloid leukemia regulated by intronicsequences of FTO
Published: August, 2023

Abstract: Iroquois transcription factor gene IRX3 is highly expressed in 20–30\% of acute myeloid leukemia (AML) and contributes to the pathognomonic differentiation block. Intron 8 FTO sequences ∼220kB downstream of I...
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Mediator 1 ablation induces enamel-to-hair lineage conversion in micethrough enhancer dynamics.
Published: July, 2023

Abstract: Postnatal cell fate is postulated to be primarily determined by the local tissue microenvironment. Here, we find that Mediator 1 (Med1) dependent epigenetic mechanisms dictate tissue-specific lineage commitment and progression of dental epithelia....
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Pre-diagnosis plasma cell-free DNA methylome profiling up to sevenyears prior to clinical detection reveals early signatures of breast cancer
Published: February, 2023

Abstract: Profiling of cell-free DNA (cfDNA) has been well demonstrated to be a potential non-invasive screening tool for early cancer detection. However, limited studies have investigated the detectability of cfDNA methylation markers that are predictive o...
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Longitudinal monitoring of cell-free DNA methylation in ALK-positivenon-small cell lung cancer patients.
Published: December, 2022

Abstract: BACKGROUND: DNA methylation (5-mC) signals in cell-free DNA (cfDNA) of cancer patients represent promising biomarkers for minimally invasive tumor detection. The high abundance of cancer-associated 5-mC alterations permits parallel and highly...
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DosR Regulates the Transcription of the Arginine BiosynthesisGene Cluster by Binding to the Regulatory Sequences inMycobacterium bovis Bacille Calmette-Guerin.
Published: November, 2022

Abstract: l-Arginine serves as a carbon and nitrogen source and is critical for (Mtb) survival in the host. Generally, ArgR acts as a repressor regulating arginine biosynthesis by binding to the promoter of the gene cluster. In this study, we report that th...
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Cell-free DNA methylation-defined prognostic subgroups in small celllung cancer identified by leukocyte methylation subtraction
Published: November, 2022

Abstract: Small cell lung cancer (SCLC) methylome is understudied. Here, we comprehensively profile SCLC using cell-free methylated DNA immunoprecipitation followed by sequencing (cfMeDIP-seq). Cell-free DNA (cfDNA) from plasma of 74 SCLC patients pre-treat...
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Identification of genomic binding sites and direct target genes for thetranscription factor DDIT3/CHOP.
Published: November, 2022

Abstract: DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicate...
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Vitamin C enhances NF-κB-driven epigenomic reprogramming andboosts the immunogenic properties of dendritic cells.
Published: October, 2022

Abstract: Dendritic cells (DCs), the most potent antigen-presenting cells, are necessary for effective activation of naïve T cells. DCs' immunological properties are modulated in response to various stimuli. Active DNA demethylation is crucial for DC d...
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The cell-free DNA methylome captures distinctions between localized andmetastatic prostate tumors.
Published: October, 2022

Abstract: Metastatic prostate cancer remains a major clinical challenge and metastatic lesions are highly heterogeneous and difficult to biopsy. Liquid biopsy provides opportunities to gain insights into the underlying biology. Here, using the highly sensit...
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Cell-wall damage activates DOF transcription factors to promote woundhealing and tissue regeneration in Arabidopsis thaliana.
Published: May, 2022

Abstract: Wound healing is a fundamental property of plants and animals that requires recognition of cellular damage to initiate regeneration. In plants, wounding activates a defense response via the production of jasmonic acid and a regeneration response v...
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Comprehensive characterization of the epigenetic landscape in Multiple Myeloma
Published: January, 2022

Abstract: Background: Human multiple myeloma (MM) cell lines (HMCLs) have been widely used to understand themolecular processes that drive MM biology. Epigenetic modifications are involved in MM development,progression, and drug resistance. A comprehensive ...
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Coordinated glucocorticoid receptor and MAFB action inducestolerogenesis and epigenome remodeling in dendritic cells
Published: January, 2022

Abstract: Abstract Glucocorticoids (GCs) exert potent anti-inflammatory effects in immune cells through the glucocorticoid receptor (GR). Dendritic cells (DCs), central actors for coordinating immune responses, acquire tolerogenic properties in response to ...
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Integrating SNPs-based genetic risk factor with blood epigenomicresponse of differentially arsenic-exposed rural subjects revealsdisease-associated signaling pathways.
Published: January, 2022

Abstract: Arsenic (As) contamination in groundwater is responsible for numerous adverse health outcomes among millions of people. Epigenetic alterations are among the most widely studied mechanisms of As toxicity. To understand how As exposure alters gene e...
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Expression of in the Stem Cell Domain Is Required for ItsFunction in the Control of Floral Meristem Activity in Arabidopsis
Published: July, 2021

Abstract: In the model plant Arabidopsis thaliana, the zinc-finger transcription factor KNUCKLES (KNU) plays an important role in the termination of floral meristem activity, a process that is crucial for preventing the overgrowth of flowers. The KNU gene i...
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Contrasting epigenetic control of transgenes and endogenous genespromotes post-transcriptional transgene silencing in
Published: May, 2021

Abstract: Transgenes that are stably expressed in plant genomes over many generations could be assumed to behave epigenetically the same as endogenous genes. Here, we report that whereas the histone H3K9me2 demethylase IBM1, but not the histone H3K4me3 deme...
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Coordinated changes in gene expression, H1 variant distribution and genome3D conformation in response to H1 depletion
Published: February, 2021

Abstract: Up to seven members of the histone H1 family may contribute to chromatin compaction and its regulation in human somatic cells. In breast cancer cells, knock-down of multiple H1 variants deregulates many genes, promotes the appearance of genome-wid...
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Histone modification dynamics at H3K27 are associated with alteredtranscription of in planta induced genes in Magnaporthe oryzae.
Published: February, 2021

Abstract: Transcriptional dynamic in response to environmental and developmental cues are fundamental to biology, yet many mechanistic aspects are poorly understood. One such example is fungal plant pathogens, which use secreted proteins and small molecules...
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A brain cyst load-associated antigen is a Toxoplasma gondii biomarker forserodetection of persistent parasites and chronic infection.
Published: February, 2021

Abstract: BACKGROUND: Biomarker discovery remains a major challenge for predictive medicine, in particular, in the context of chronic diseases. This is true for the widespread protozoan Toxoplasma gondii which establishes long-lasting parasitism in metazoan...
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Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer.
Published: July, 2020

Abstract: BACKGROUND: The high lethal rate of pancreatic cancer is partly due to a lack of efficient biomarkers for screening and early diagnosis. We attempted to develop effective and noninvasive methods using 5-methylcytosine (5mC) and 5-hydroxymethylcyto...
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Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes.
Published: June, 2020

Abstract: Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) is a highly sensitive assay capable of detecting early-s...
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Removal of H2Aub1 by ubiquitin-specific proteases 12 and 13 is required for stable Polycomb-mediated gene repression in Arabidopsis.
Published: June, 2020

Abstract: BACKGROUND: Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylat...
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A Germline Mutation in the Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer.
Published: June, 2020

Abstract: Non-medullary thyroid cancer (NMTC) is a common endocrine malignancy with a genetic basis that has yet to be unequivocally established. In a recent whole-genome sequencing study of five families with occurrence of NMTCs, we shortlisted promising v...
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UNBRANCHED3 Expression and Inflorescence Development is Mediated by UNBRANCHED2 and the Distal Enhancer, KRN4, in Maize.
Published: April, 2020

Abstract: Enhancers are cis-acting DNA segments with the ability to increase target gene expression. They show high sensitivity to DNase and contain specific DNA elements in an open chromatin state that allows the binding of transcription factors (TFs). Whi...
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Differential modulation of the androgen receptor for prostate cancer therapy depends on the DNA response element.
Published: March, 2020

Abstract: Androgen receptor (AR) action is a hallmark of prostate cancer (PCa) with androgen deprivation being standard therapy. Yet, resistance arises and aberrant AR signaling promotes disease. We sought compounds that inhibited genes driving cancer but n...
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A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment.
Published: February, 2020

Abstract: Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on ch...
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Seviteronel, a Novel CYP17 Lyase Inhibitor and Androgen Receptor Antagonist, Radiosensitizes AR-Positive Triple Negative Breast Cancer Cells
Published: February, 2020

Abstract: Increased rates of locoregional recurrence (LR) have been observed in triple negative breast cancer (TNBC) despite multimodality therapy, including radiation (RT). Recent data suggest inhibiting the androgen receptor (AR) may be an effective radio...
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Ikaros antagonizes DNA binding by STAT5 in pre-B cells.
Published: January, 2020

Abstract: The IKZF1 gene, which encodes the Ikaros transcription factor, is frequently deleted or mutated in patients with B-cell precursor acute lymphoblastic leukemias that express oncogenes, like BCR-ABL, which activate the JAK-STAT5 pathway. Ikaros func...
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Identification and Massively Parallel Characterization of Regulatory Elements Driving Neural Induction
Published: November, 2019

Abstract: Epigenomic regulation and lineage-specific gene expression act in concert to drive cellular differentiation, but the temporal interplay between these processes is largely unknown. Using neural induction from human pluripotent stem cells (hPSCs) as...
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Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Published: November, 2019

Abstract: Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that r...
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Epigenetic down-regulation of the HIST1 locus predicts better prognosis in acute myeloid leukemia with NPM1 mutation.
Published: October, 2019

Abstract: BACKGROUND: The epigenetic machinery is frequently altered in acute myeloid leukemia. Focusing on cytogenetically normal (CN) AML, we previously described an abnormal H3K27me3 enrichment covering 70 kb on the HIST1 cluster (6.p22) in CN-AML p...
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Preparation of cfMeDIP-seq libraries for methylome profiling of plasma cell-free DNA.
Published: August, 2019

Abstract: Circulating cell-free DNA (cfDNA) comprises small DNA fragments derived from normal and tumor tissue that are released into the bloodstream. Recently, methylation profiling of cfDNA as a liquid biopsy tool has been gaining prominence due to the pr...
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EZH2 as a novel therapeutic target for atrial fibrosis and atrial fibrillation.
Published: August, 2019

Abstract: Angiotensin II (Ang-II)-induced fibroblast differentiation plays an important role in the development of atrial fibrosis and atrial fibrillation (AF). Here, we show that the expression of the histone methyltransferase enhancer of zeste homolog 2 (...
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Clinicopathological evaluation of PD-L1 expression and cytotoxic T-lymphocyte infiltrates across intracranial molecular subgroups of ependymomas: are these tumors potential candidates for immune check-point blockade?
Published: August, 2019

Abstract: Immune check-point blockade (ICB) targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has created paradigm shift in cancer treatment. 'ST-RELA' and 'PF-A' molecular subgroups of ependymomas (EPN) show poor outcomes. We ...
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The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2.
Published: July, 2019

Abstract: The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which s...
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A TetR-family transcription factor regulates fatty acid metabolism in the archaeal model organism Sulfolobus acidocaldarius.
Published: April, 2019

Abstract: Fatty acid metabolism and its regulation are known to play important roles in bacteria and eukaryotes. By contrast, although certain archaea appear to metabolize fatty acids, the regulation of the underlying pathways in these organisms remains unc...
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EZH2 is overexpressed in transitional preplasmablasts and is involved in human plasma cell differentiation.
Published: February, 2019

Abstract: Plasma cells (PCs) play a major role in the defense of the host organism against pathogens. We have shown that PC generation can be modeled using multi-step culture systems that reproduce the sequential cell differentiation occurring in vivo. Usin...
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Protocols for Genetic and Epigenetic Studies of Rare Diseases Affecting Dental Tissues.
Published: January, 2019

Abstract: This chapter describes methods related to the diagnosis of genetic dental diseases. Based on the present knowledge, clinical phenotyping and next-generation sequencing techniques are discussed. Methods necessary for Sanger sequencing, multiplex li...
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Sensitive tumour detection and classification using plasma cell-free DNA methylomes.
Published: November, 2018

Abstract: The use of liquid biopsies for cancer detection and management is rapidly gaining prominence. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these method...
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RbAp48 Protein Is a Critical Component of GPR158/OCN Signaling and Ameliorates Age-Related Memory Loss.
Published: October, 2018

Abstract: Precisely deciphering the molecular mechanisms of age-related memory loss is crucial to create appropriate therapeutic interventions. We have previously shown that the histone-binding protein RbAp48/Rbbp4 is a molecular determinant of Age-Related ...
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Convergent evolution of complex genomic rearrangements in two fungal meiotic drive elements.
Published: October, 2018

Abstract: Meiotic drive is widespread in nature. The conflict it generates is expected to be an important motor for evolutionary change and innovation. In this study, we investigated the genomic consequences of two large multi-gene meiotic drive elements, S...
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IFN-γ immune priming of macrophages in vivo induces prolonged STAT1 binding and protection against Cryptococcus neoformans.
Published: October, 2018

Abstract: Development of vaccines against opportunistic infections is difficult as patients most at risk of developing disease are deficient in aspects of the adaptive immune system. Here, we utilized an experimental immunization strategy to induce innate m...
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PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs.
Published: October, 2018

Abstract: BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer develop...
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Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo.
Published: October, 2018

Abstract: Proteomic analysis of histones has shown that they are subject to a superabundance of acylations, which extend far beyond acetylation, to include: crotonylation, propionylation, butyrylation, malonylation, succinylation, β-hydroxybutyrylation...
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Identification of miR-379/miR-656 (C14MC) cluster downregulation and associated epigenetic and transcription regulatory mechanism in oligodendrogliomas.
Published: August, 2018

Abstract: INTRODUCTION: Although role of individual microRNAs (miRNAs) in the pathogenesis of gliomas has been well studied, their role as a clustered remains unexplored in gliomas. METHODS: In this study, we performed the expression analysis of miR-379/miR...
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Epigenetic regulation of brain region-specific microglia clearance activity.
Published: August, 2018

Abstract: The rapid elimination of dying neurons and nonfunctional synapses in the brain is carried out by microglia, the resident myeloid cells of the brain. Here we show that microglia clearance activity in the adult brain is regionally regulated and depe...
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An improved assembly and annotation of the melon (Cucumis melo L.) reference genome.
Published: May, 2018

Abstract: We report an improved assembly (v3.6.1) of the melon (Cucumis melo L.) genome and a new genome annotation (v4.0). The optical mapping approach allowed correcting the order and the orientation of 21 previous scaffolds and permitted to correctly def...
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Polycomb Repressive Complex 2 attenuates the very high expression of the Arabidopsis gene NRT2.1.
Published: May, 2018

Abstract: PRC2 is a major regulator of gene expression in eukaryotes. It catalyzes the repressive chromatin mark H3K27me3, which leads to very low expression of target genes. NRT2.1, which encodes a key root nitrate transporter in Arabidopsis, is targeted b...
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p27 regulates alpha-synuclein expression.
Published: March, 2018

Abstract: Alpha-synuclein (α-SYN) is the main component of anomalous protein aggregates (Lewy bodies) that play a crucial role in several neurodegenerative diseases (synucleinopathies) like Parkinson's disease and multiple system atrophy. However, the...
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Chromatin Immunoprecipitation Assay in the Hyperthermoacidophilic Crenarchaeon, Sulfolobus acidocaldarius.
Published: January, 2018

Abstract: Chromatin immunoprecipitation (ChIP) is a powerful method used for identifying genome-wide DNA-protein interactions in vivo. A large number of essential intracellular processes such as DNA replication, transcription regulation, chromatin stability...
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ChIP-Seq analysis identifies p27(Kip1)-target genes involved in cell adhesion and cell signalling in mouse embryonic fibroblasts
Published: November, 2017

Abstract: The protein p27Kip1 (p27), a member of the Cip-Kip family of cyclin-dependent kinase inhibitors, is involved in tumorigenesis and a correlation between reduced levels of this protein in human tumours and a worse prognosis has been established. Rec...
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PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways
Published: November, 2017

Abstract: In NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting of these receptors is yet to be achieved. In this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster and miR-125a-5p are dow...
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Data on novel DNA methylation changes induced by valproic acid in human hepatocytes
Published: November, 2017

Abstract: Valproic acid (VPA) is a widely prescribed antiepileptic drug in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis. However the exact mechanism of the steatosis formation is unknown. The data presented in...
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Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes
Published: October, 2017

Abstract: Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis through mitochondrial dysfunction. The aim of this study is to further inv...
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Distinguishing States of Arrest: Genome-Wide Descriptions of Cellular Quiescence Using ChIP-Seq and RNA-Seq Analysis.
Published: October, 2017

Abstract: Regenerative potential in adult stem cells is closely associated with the establishment of-and exit from-a temporary state of quiescence. Emerging evidence not only provides a rationale for the link between lineage determination programs and cell ...
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High-Resolution Chromatin Immunoprecipitation: ChIP-Sequencing
Published: September, 2017

Abstract: Chromatin immunoprecipitation (ChIP) coupled with next-generation sequencing (NGS) is widely used for studying the nucleoprotein components that are involved in the various cellular processes required for shaping the bacterial nucleoid. This metho...
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Epigenome profiling and editing of neocortical progenitor cells during development
Published: September, 2017

Abstract: The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC ty...
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Plant-Specific Histone Deacetylases HDT1/2 Regulate GIBBERELLIN 2-OXIDASE2 Expression to Control Arabidopsis Root Meristem Cell Number
Published: September, 2017

Abstract: Root growth is modulated by environmental factors and depends on cell production in the root meristem (RM). New cells in the meristem are generated by stem cells and transit-amplifying cells, which together determine RM cell number. Transcription ...
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MAPK-triggered chromatin reprogramming by histone deacetylase in plant innate immunity
Published: July, 2017

Abstract: Background Microbial-associated molecular patterns activate several MAP kinases, which are major regulators of the innate immune response in Arabidopsis thaliana that induce large-scale changes in gene expression. Here, we determine whether m...
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The Arabidopsis SWI/SNF protein BAF60 mediates seedling growth control by modulating DNA accessibility
Published: June, 2017

Abstract: Background Plant adaptive responses to changing environments involve complex molecular interplays between intrinsic and external signals. Whilst much is known on the signaling components mediating diurnal, light, and temperature controls on p...
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LRP8-Reelin-Regulated Neuronal Enhancer Signature Underlying Learning and Memory Formation
Published: May, 2017

Abstract: One of the exceptional properties of the brain is its ability to acquire new knowledge through learning and to store that information through memory. The epigenetic mechanisms linking changes in neuronal transcriptional programs to behavioral plas...
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PPARγ Links BMP2 and TGFβ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism
Published: May, 2017

Abstract: BMP2 and TGFβ1 are functional antagonists of pathological remodeling in the arteries, heart, and lung; however, the mechanisms in VSMCs, and their disturbance in pulmonary arterial hypertension (PAH), are unclear. We found a pro-prolifer...
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sgs1: a neomorphic nac52 allele impairing PTGS through SGS3 down-regulation
Published: May, 2017

Abstract: Post-transcriptional gene silencing (PTGS) is a defense mechanism that targets invading nucleic acids from endogenous (transposons) or exogenous (pathogens, transgenes) sources. Genetic screens based on the reactivation of silenced transgenes have...
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Liver receptor homolog-1 (NR5a2) regulates CD95/Fas ligand transcription and associated T-cell effector functions.
Published: April, 2017

Abstract: CD95/Fas ligand (FasL) is a cell death-promoting member of the tumor necrosis factor family with important functions in the regulation of T-cell homeostasis and cytotoxicity. In T cells, FasL expression is tightly regulated on a transcriptional le...
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Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer
Published: April, 2017

Abstract: Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a crit...
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Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia
Published: April, 2017

Abstract: The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become a...
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Type I interferon-enhanced IL-10 expression in human CD4 T cells is regulated by STAT3, STAT2, and BATF transcription factors
Published: February, 2017

Abstract: Type I IFN can exert pro- and anti-inflammatory activities in the immune system. Here, we have investigated the mechanism by which IFN-α enhances early expression of the anti-inflammatory cytokine IL-10 in human CD45RA+CD4+ T cells. With the...
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H3K23me1 is an evolutionarily conserved histone modification associated with CG DNA methylation in Arabidopsis
Published: February, 2017

Abstract: Amino-terminal tails of histones are targets for diverse post-translational modifications whose combinatorial action may constitute a code that will be read and interpreted by cellular proteins to define particular transcriptional states. Here, we...
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Applying the INTACT method to purify endosperm nuclei and to generate parental-specific epigenome profiles.
Published: February, 2017

Abstract: The early endosperm tissue of dicot species is very difficult to isolate by manual dissection. This protocol details how to apply the INTACT (isolation of nuclei tagged in specific cell types) system for isolating early endosperm nuclei of Arabido...
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Nitric oxide modulates histone acetylation at stress genes by inhibition of histone deacetylases
Published: December, 2016

Abstract: Histone acetylation, which is an important mechanism to regulate gene expression, is controlled by the opposing action of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In animals, several HDACs are subjected to regulation by ...
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Genomic Characterization of Metformin Hepatic Response
Published: November, 2016

Abstract: Metformin is used as a first-line therapy for type 2 diabetes (T2D) and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and...
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Transcriptional Activation of Pericentromeric Satellite Repeats and Disruption of Centromeric Clustering upon Proteasome Inhibition
Published: November, 2016

Abstract: Heterochromatinisation of pericentromeres, which in mice consist of arrays of major satellite repeats, are important for centromere formation and maintenance of genome stability. The dysregulation of this process has been linked to genomic stress ...
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The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression
Published: September, 2016

Abstract: Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes...
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Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing
Published: September, 2016

Abstract: Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed g...
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Dynamic Interplay between the Transcriptome and Methylome in Response to Oxidative and Alkylating Stress
Published: August, 2016

Abstract: In recent years, it has been shown that free radicals not only react directly with DNA but also regulate epigenetic processes such as DNA methylation, which may be relevant within the context of, for example, tumorigenesis. However, how these free...
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Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster
Published: August, 2016

Abstract: Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotyp...
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Genome-wide DNA methylation profiling with MeDIP-seq using archived dried blood spots
Published: July, 2016

Abstract: Background In utero and early-life experienced environmental exposures are suggested to play an important role in many multifactorial diseases potentially mediated through lasting effects on the epigenome. As the epigenome in addition remains modi...
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Parental epigenetic asymmetry of PRC2-mediated histone modifications in the Arabidopsis endosperm
Published: April, 2016

Abstract: Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manus...
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Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death
Published: February, 2016

Abstract: Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a ...
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Targeting the MLL complex in castration-resistant prostate cancer.
Published: April, 2015

Abstract: Resistance to androgen deprivation therapies and increased androgen receptor (AR) activity are major drivers of castration-resistant prostate cancer (CRPC). Although prior work has focused on targeting AR directly, co-activators of AR signaling, w...
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Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells
Published: December, 2014

Abstract: The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex viv...
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Sperm DNA Methylation Analysis in Swine Reveals Conserved and Species-Specific Methylation Patterns and Highlights an Altered Methylation at the GNAS Locus in Infertile Boars.
Published: October, 2014

Abstract: Male infertility is an increasing health issue in today's society, for both human or livestock populations. In livestock, male infertility slows the improvement of animal selection programs and agricultural productivity. There are increasing evide...
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SOX11 promotes tumor angiogenesis through transcriptional regulation of PDGFA in mantle cell lymphoma.
Published: October, 2014

Abstract: SOX11 is overexpressed in several solid tumors and in the vast majority of aggressive mantle cell lymphomas (MCLs). We have recently proven that SOX11 silencing reduces tumor growth in a MCL xenograft model, consistent with the indolent clinical c...
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The pro-apoptotic activity of Drosophila Rbf1 involves dE2F2-dependent downregulation of diap1 and buffy mRNA.
Published: September, 2014

Abstract: The retinoblastoma gene, rb, ensures at least its tumor suppressor function by inhibiting cell proliferation. Its role in apoptosis is more complex and less described than its role in cell cycle regulation. Rbf1, the Drosophila homolog of Rb, has ...
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Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development.
Published: September, 2014

Abstract: Cardiac development arises from two sources of mesoderm progenitors, the first heart field (FHF) and the second (SHF). Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors common for both heart fields. Here, using clo...
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Noncoding Transcription by Alternative RNA Polymerases Dynamically Regulates an Auxin-Driven Chromatin Loop.
Published: July, 2014

Abstract: The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidop...
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Distribution of segmental duplications in the context of higher order chromatin organisation of human chromosome 7.
Published: June, 2014

Abstract: BACKGROUND: Segmental duplications (SDs) are not evenly distributed along chromosomes. The reasons for this biased susceptibility to SD insertion are poorly understood. Accumulation of SDs is associated with increased genomic instability, which ca...
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Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer.
Published: June, 2014

Abstract: Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. Progression to CRPC after androgen ablation therapy is predominantly driven by deregulated androgen receptor (AR) signalling. Despite the suc...
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Seminoma and embryonal carcinoma footprints identified by analysis of integrated genome-wide epigenetic and expression profiles of germ cell cancer cell lines.
Published: June, 2014

Abstract: BACKGROUND: Originating from Primordial Germ Cells/gonocytes and developing via a precursor lesion called Carcinoma In Situ (CIS), Germ Cell Cancers (GCC) are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS). ...
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BarR, an Lrp-type transcription factor in Sulfolobus acidocaldarius, regulates an aminotransferase gene in a β-alanine responsive manner.
Published: May, 2014

Abstract: In archaea, nothing is known about the β-alanine degradation pathway or its regulation. In this work, we identify and characterize BarR, a novel Lrp-like transcription factor and the first one that has a non-proteinogenic amino acid ligand. BarR i...
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Mapping of six somatic linker histone H1 variants in human breast cancer cells uncovers specific features of H1.2.
Published: April, 2014

Abstract: Seven linker histone H1 variants are present in human somatic cells with distinct prevalence across cell types. Despite being key structural components of chromatin, it is not known whether the different variants have specific roles in the regulat...
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Contesting the dogma of an age-related heat shock response impairment: implications for cardiac-specific age-related disorders.
Published: March, 2014

Abstract: Ageing is associated with the reduced performance of physiological processes and has been proposed as a major risk factor for disease. An age-related decline in stress response pathways has been widely documented in lower organisms. In particular,...
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The BAF60 Subunit of the SWI/SNF Chromatin-Remodeling Complex Directly Controls the Formation of a Gene Loop at FLOWERING LOCUS C in Arabidopsis.
Published: February, 2014

Abstract: SWI/SNF complexes mediate ATP-dependent chromatin remodeling to regulate gene expression. Many components of these complexes are evolutionarily conserved, and several subunits of Arabidopsis thaliana SWI/SNF complexes are involved in the control o...
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The cohesin complex regulates immunoglobulin class switch recombination.
Published: November, 2013

Abstract: Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to switch regions and by the subsequent generation of double-stranded DNA breaks (DSBs). Thes...
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The Elongin Complex Antagonizes the Chromatin Factor Corto for Vein versus Intervein Cell Identity in Drosophila Wings.
Published: October, 2013

Abstract: Drosophila wings mainly consist of two cell types, vein and intervein cells. Acquisition of either fate depends on specific expression of genes that are controlled by several signaling pathways. The nuclear mechanisms that translate signaling into...
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Cbl-b mediates TGFβ sensitivity by downregulating inhibitory SMAD7 in primary T cells.
Published: June, 2013

Abstract: T cell-intrinsic transforming growth factor β (TGFβ) receptor signaling plays an essential role in controlling immune responses. The RING-type E3 ligase Cbl-b has been shown to mediate the sensitivity of T cells to TGFβ; however, the mechanism und...
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Nuclear retention of the transcription factor NLP7 orchestrates the early response to nitrate in plants.
Published: April, 2013

Abstract: Nitrate is both an important nutrient and a signalling molecule for plants. Although several components of the nitrate signalling pathway have been identified, their hierarchical organization remains unclear. Here we show that the localization of ...
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Multiple functions of Kip-related protein5 connect endoreduplication and cell elongation.
Published: April, 2013

Abstract: Despite considerable progress in our knowledge regarding the cell cycle inhibitor of the Kip-related protein (KRP) family in plants, less is known about the coordination of endoreduplication and cell differentiation. In animals, the role of cyclin...
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Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation.
Published: March, 2013

Abstract: Type II DNA topoisomerases catalyse DNA double-strand cleavage, passage and re-ligation to effect topological changes. There is considerable interest in elucidating topoisomerase II roles, particularly as these proteins are targets for anti-cancer...
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Linking proteomic and transcriptional data through the interactome and epigenome reveals a map of oncogene-induced signaling.
Published: February, 2013

Abstract: Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study eac...
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Dual function of MIPS1 as a metabolic enzyme and transcriptional regulator.
Published: January, 2013

Abstract: Because regulation of its activity is instrumental either to support cell proliferation and growth or to promote cell death, the universal myo-inositol phosphate synthase (MIPS), responsible for myo-inositol biosynthesis, is a critical enzyme of p...
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New partners in regulation of gene expression: the enhancer of trithorax and polycomb corto interacts with methylated ribosomal protein l12 via its chromodomain.
Published: October, 2012

Abstract: Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and ...
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Nuclear orphan receptor NR2F6 directly antagonizes NFAT and RORγt binding to the Il17a promoter.
Published: August, 2012

Abstract: Interleukin-17A (IL-17A) is the signature cytokine produced by Th17 CD4(+) T cells and has been tightly linked to autoimmune pathogenesis. In particular, the transcription factors NFAT and RORγt are known to activate Il17a transcription, although ...
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The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo.
Published: June, 2012

Abstract: The CACCC-box binding protein Erythroid Krüppel-like Factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of a second Klf, Basic Krüppel-lik...
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Global analysis of the regulon of the transcriptional repressor LexA, a key component of the SOS response in Mycobacterium tuberculosis.
Published: April, 2012

Abstract: The DNA damage response is crucial for bacterial survival. The transcriptional repressor LexA is a key component of the SOS response, the main mechanism for the regulation of DNA repair genes in many bacteria. In contrast, in mycobacteria gene ind...
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TNFR1 is essential for CD40, but not for lipopolysaccharide-induced sickness behavior and clock gene dysregulation.
Published: March, 2011

Abstract: Autoimmune and infectious diseases are associated with behavioral changes referred to as sickness behavior syndrome (SBS). In autoimmunity, the generation of anti-self T lymphocytes and autoantibodies critically involves binding of CD40 ligand on ...
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Control of flowering and cell fate by LIF2, an RNA binding partner of the polycomb complex component LHP1.
Published: January, 2011

Abstract: Polycomb Repressive Complexes (PRC) modulate the epigenetic status of key cell fate and developmental regulators in eukaryotes. The chromo domain protein like heterochromatin protein1 (LHP1) is a subunit of a plant PRC1-like complex in Arabidopsis...
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Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression.

Abstract: Alterations in DNA methylation have been associated with genome-wide hypomethylation and regional de novo methylation in numerous cancers. De novo methylation is mediated by the de novo methyltransferases Dnmt3a and 3b, but only Dnmt3b has been im...
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