The genetic landscape of origins of replication in P. falciparum Published: December, 2023 Abstract:
Various origin mapping approaches have enabled genome-wide identification of origins of replication (ORI) in model organisms, but only a few studies have focused on divergent organisms. By employing three complementary approaches we provide a high... Read more »
Gene Regulatory Interactions at Lamina-Associated Domains Published: January, 2023 Abstract:
The nuclear lamina provides a repressive chromatin environment at the nuclear periphery. However, whereas most genes in lamina-associated domains (LADs) are inactive, over ten percent reside in local euchromatic contexts and are expressed. How the... Read more »
Dominant role of DNA methylation over H3K9me3 for IAP silencingin endoderm. Published: September, 2022 Abstract:
Silencing of endogenous retroviruses (ERVs) is largely mediated by repressive chromatin modifications H3K9me3 and DNA methylation. On ERVs, these modifications are mainly deposited by the histone methyltransferase Setdb1 and by the maintenance DNA... Read more »
Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes Published: May, 2022 Abstract:
Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used... Read more »
NuA4 and H2A.Z control environmental responses and autotrophicgrowth in Arabidopsis Published: January, 2022 Abstract:
Nucleosomal acetyltransferase of H4 (NuA4) is an essential transcriptional coactivator in eukaryotes, but remains poorly characterized in plants. Here, we describe Arabidopsis homologs of the NuA4 scaffold proteins Enhancer of Polycomb-Like 1 (AtE... Read more »
Extensive NEUROG3 occupancy in the human pancreatic endocrine generegulatory network. Published: November, 2021 Abstract:
OBJECTIVE: Mice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin-secreting beta cells, the absence of which leads to diabetes. In humans, homozygous mutations of NEUROG3 manifest with neonata... Read more »
INTS11 regulates hematopoiesis by promoting PRC2 function. Published: September, 2021 Abstract:
INTS11, the catalytic subunit of the Integrator (INT) complex, is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. However, the role of INTS11 in hematopoietic stem and progenitor cell (HSPC) biology is unknown. Here, we report ... Read more »
Altered Chromatin States Drive Cryptic Transcription in AgingMammalian Stem Cells. Published: August, 2021 Abstract:
A repressive chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation suppresses cryptic transcription in embryonic stem cells. Cryptic transcription is elevated with age in yeast and nematodes, and reducing i... Read more »
Waves of sumoylation support transcription dynamics during adipocytedifferentiation Published: April, 2021 Abstract:
Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, little is known about the mechanisms that orchestrate the dramatic transcri... Read more »
Loss of SETD1B results in the redistribution of genomic H3K4me3 in theoocyte Published: March, 2021 Abstract:
Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransfe... Read more »
Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture. Published: December, 2020 Abstract:
Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction, although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms B-E (H1B, H1C, H1D and H1E; also known as H1-5, H1-2, H1-... Read more »
The gut microbiome switches mutant p53 from tumour-suppressive tooncogenic. Published: July, 2020 Abstract:
Somatic mutations in p53, which inactivate the tumour-suppressor function of p53 and often confer oncogenic gain-of-function properties, are very common in cancer. Here we studied the effects of hotspot gain-of-function mutations in Trp53 (the gen... Read more »
HDAC3 functions as a positive regulator in Notch signal transduction. Published: February, 2020 Abstract:
Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the N... Read more »
Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon. Published: February, 2020 Abstract:
Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap... Read more »
An inferred fitness consequence map of the rice genome. Published: February, 2020 Abstract:
The extent to which sequence variation impacts plant fitness is poorly understood. High-resolution maps detailing the constraint acting on the genome, especially in regulatory sites, would be beneficial as functional annotation of noncoding sequen... Read more »
Distinct CoREST complexes act in a cell-type-specific manner. Published: November, 2019 Abstract:
CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use p... Read more »
Development and epigenetic plasticity of murine Müller glia. Published: July, 2019 Abstract:
The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of Müller glia. To understand the role of mammalian Müller glia as a source of progen... Read more »
Guidelines for optimized gene knockout using CRISPR/Cas9 Published: May, 2019 Abstract:
CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by... Read more »
Differential regulation of RNA polymerase III genes during liver regeneration. Published: February, 2019 Abstract:
Mouse liver regeneration after partial hepatectomy involves cells in the remaining tissue synchronously entering the cell division cycle. We have used this system and H3K4me3, Pol II and Pol III profiling to characterize adaptations in Pol III tra... Read more »
Genome-wide rules of nucleosome phasing Published: June, 2018 Abstract:
Regular successions of positioned nucleosomes – phased nucleosome arrays (PNAs) – are predominantly known from transcriptional start sites (TSS). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inv... Read more »
Genome-wide analysis of PDX1 target genes in human pancreatic progenitors. Published: March, 2018 Abstract:
OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the... Read more »
MLL2 conveys transcription-independent H3K4 trimethylation in oocytes Published: January, 2018 Abstract:
Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyt... Read more »
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... Read more »
Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae Published: April, 2017 Abstract:
Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG prote... Read more »
Crebbp loss cooperates with Bcl2 over-expression to promote lymphoma in mice Published: March, 2017 Abstract:
CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can coope... Read more »
The Drosophila speciation factor HMR localizes to genomic insulator sites Published: February, 2017 Abstract:
Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr and Lhr genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription ... Read more »
PionX sites mark the X chromosome for dosage compensation Published: August, 2016 Abstract:
The rules defining which small fraction of related DNA sequences can be selectively bound by a transcription factor are poorly understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require th... Read more »
Sepsis induces specific changes in histone modification patterns in human monocytes. Published: March, 2015 Abstract:
BACKGROUND: Sepsis is a global burden and the primary cause of death in intensive care units worldwide. The pathophysiological changes induced by the host's systemic inflammatory response to infection are not yet fully understood. During sepsis, t... Read more »
