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Histone lysine demethylase inhibition reprograms prostate cancermetabolism and mechanics.
Chianese Ugo and Papulino Chiara and Passaro Eugenia andEvers Tom Mj and Babaei Mehrad and Toraldo Antonella andDe Marchi Tommaso and Niméus Emma and Carafa Vincenzo andNicoletti Maria Maddalena and Del Gaudio Nunzio andIaccarino Nunzia an
OBJECTIVE: Aberrant activity of androgen receptor (AR) is the primary cause underlying development and progression of prostate cancer (PCa) and castration-resistant PCa (CRPC). Androgen signaling regulates gene transcription and lipid metabolism, facilitating tumor growth and therapy resistance in early and advanced... |
Comprehensive characterization of the epigenetic landscape in Multiple Myeloma
Elina Alaterre et al.
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 characterization of the epigenetic landscape of MM wouldadvance our un... |
Chromatin dysregulation associated with NSD1 mutation in head and necksquamous cell carcinoma.
Farhangdoost, Nargess et al.
Chromatin dysregulation has emerged as an important mechanism of oncogenesis. To develop targeted treatments, it is important to understand the transcriptomic consequences of mutations in chromatin modifier genes. Recently, mutations in the histone methyltransferase gene nuclear receptor binding SET domain protein 1... |
The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity
Domínguez-Andrés Jorge, Novakovic Boris, Li Yang, Scicluna Brendon P., Gresnigt Mark S., Arts Rob J.W., Oosting Marije, Moorlag Simone J.C.F.M., Groh Laszlo A., Zwaag Jelle, Koch Rebecca M., ter Horst Rob, Joosten Leo A.B., Wijmenga Cisca, Michelucci Ales
Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which subsequently mediated innate immune tolerance in human monocytes. In con... |
Interplay of cell–cell contacts and RhoA/MRTF‐A signaling regulates cardiomyocyte identity
Dorn et al
Cell–cell and cell–matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell–cell contacts at the intercalated disk connect... |
Viral targeting of TFIIB impairs de novo polymerase II recruitment and affects antiviral immunity
Darya A. Haas, Arno Meiler, Katharina Geiger, Carola Vogt, Ellen Preuss, Georg Kochs, Andreas Pichlmair
Viruses have evolved a plethora of mechanisms to target host antiviral responses. Here, we propose a yet uncharacterized mechanism of immune regulation by the orthomyxovirus Thogoto virus (THOV) ML protein through engaging general transcription factor TFIIB. ML generates a TFIIB depleted nuclear environment by re-lo... |
HMGB2 Loss upon Senescence Entry Disrupts Genomic Organization and Induces CTCF Clustering across Cell Types
Zirkel et. al.
Processes like cellular senescence are characterized by complex events giving rise to heterogeneous cell populations. However, the early molecular events driving this cascade remain elusive. We hypothesized that senescence entry is triggered by an early disruption of the cells’ three-dimensional (3D) ... |
Widespread bacterial protein histidine phosphorylation revealed by mass spectrometry-based proteomics
Clement M Potel, Miao-Hsia Lin, Albert J R Heck, Simone Lemeer
For decades, major difficulties in analyzing histidine phosphorylation have limited the study of phosphohistidine signaling. Here we report a method revealing widespread and abundant protein histidine phosphorylation in Escherichia coli. We generated an extensive E. coli phosphoproteome data set, in which a remarkab... |
MEIS homeodomain proteins facilitate PARP1/ARTD1-mediated eviction of histone H1
Ann-Christin Hau, Britta Moyo Grebbin, Zsuzsa Agoston, Marie Anders-Maurer, Tamara Müller, Anja Groß, Jasmine Kolb, Julian D. Langer, Claudia Döring, Dorothea Schulte
Pre–B-cell leukemia homeobox (PBX) and myeloid ecotropic viral integration site (MEIS) proteins control cell fate decisions in many physiological and pathophysiological contexts, but how these proteins function mechanistically remains poorly defined. Focusing on the first hours of neuronal differentiation of a... |
reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells
Kinkley S et al.
The combinatorial action of co-localizing chromatin modifications and regulators determines chromatin structure and function. However, identifying co-localizing chromatin features in a high-throughput manner remains a technical challenge. Here we describe a novel reChIP-seq approach and tailored bioinformatic analys... |
UMI-4C for quantitative and targeted chromosomal contact profiling
Omer Schwartzman, Zohar Mukamel, Noa Oded-Elkayam, Pedro Olivares-Chauvet, Yaniv Lubling, Gilad Landan, Shai Izraeli and Amos Tanay
We developed a targeted chromosome conformation capture (4C) approach that uses unique molecular identifiers (umis) to derive high-complexity quantitative chromosome contact profiles with controlled signal-to-noise ratios. UMI-4C detects chromosomal interactions with improved sensitivity and specificity, and it can ... |
Histamine 1 receptor-Gβγ-cAMP/PKA-CFTR pathway mediates the histamine-induced resetting of the suprachiasmatic circadian clock
Yoon Sik Kim, Young-Beom Kim, Woong Bin Kim, Seung Won Lee, Seog Bae Oh, Hee-Chul Han, C. Justin LeeEmail author, Christopher S. Colwell and Yang In Kim
Background
Recent evidence indicates that histamine, acting on histamine 1 receptor (H1R), resets the circadian clock in the mouse suprachiasmatic nucleus (SCN) by increasing intracellular Ca2+ concentration ([Ca2+]i) through the activation of CaV1.3 L-type Ca2+ channels and Ca2+-induced Ca2+ release from ryan... |
Standardizing chromatin research: a simple and universal method for ChIP-seq
Laura Arrigoni, Andreas S. Richter, Emily Betancourt, Kerstin Bruder, Sarah Diehl, Thomas Manke and Ulrike Bönisch
Here we demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (Nuclei Extraction by Sonication) that is highly effective across various organisms, cell ... |
HNF1β drives glutathione (GSH) synthesis underlying intrinsic carboplatin resistance of ovarian clear cell carcinoma (OCCC)
Filipa Lopes-Coelho, Sofia Gouveia-Fernandes, Luís G Gonçalves, Carolina Nunes, Inês Faustino, Fernanda Silva, Ana Félix, Sofia A Pereira, Jacinta Serpa
Chemoresistance to platinum-based antineoplastic agents is a consistent feature among ovarian carcinomas; however, whereas high-grade serous carcinoma (OSC) acquires resistance during chemotherapy, ovarian clear cell carcinoma (OCCC) is intrinsically resistant. The main objective of this study was to explore, in vit... |
LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2
Maryem A. Hussein, Elina Shrestha, Mireille Ouimet, Tessa J. Barrett, Sarah Leone, Kathryn J. Moore, Yann Hérault, Edward A. Fisher, Michael J. Garabedian
High cholesterol and diabetes are major risk factors for atherosclerosis. Regression of atherosclerosis is mediated in part by the Liver X Receptor (LXR) through the induction of genes involved in cholesterol transport and efflux. In the context of diabetes, regression of atherosclerosis is impaired. We proposed tha... |
Sensitive detection of chromatin-altering polymorphisms reveals autoimmune disease mechanisms.
Del Rosario RC, Poschmann J, Rouam SL, Png E, Khor CC, Hibberd ML, Prabhakar S
Most disease associations detected by genome-wide association studies (GWAS) lie outside coding genes, but very few have been mapped to causal regulatory variants. Here, we present a method for detecting regulatory quantitative trait loci (QTLs) that does not require genotyping or whole-genome sequencing. The method... |
Population differentiation determined from putative neutral and divergent adaptive genetic markers in Eulachon (Thaleichthys pacificus, Osmeridae), an anadromous Pacific smelt.
Candy JR, Campbell NR, Grinnell MH, Beacham TD, Larson WA, Narum SR
Twelve eulachon (Thaleichthys pacificus, Osmeridae) populations ranging from Cook Inlet, Alaska and along the west coast of North America to the Columbia River were examined by restriction-site-associated DNA (RAD) sequencing to elucidate patterns of neutral and adaptive variation in this high geneflow species. A to... |
Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling.
Caixia Guo,1,2 Yinye Xia,1,2 Piye Niu,1,2 Lizhen Jiang,1,2 Junchao Duan,1,2 Yang Yu,1,2 Xianqing Zhou,1,2 Yanbo Li,1,2 Zhiwei Sun1,2
Abstract: Despite the widespread application of silica nanoparticles (SiNPs) in industrial, commercial, and biomedical fields, their response to human cells has not been fully elucidated. Overall, little is known about the toxicological effects of SiNPs on the cardiovascular system. In this study, SiNPs with a ... |
Step-by-step preparation of proteins for mass spectrometric analysis.
Franz T, Li X.
Nowadays, identification of proteins from biological samples by mass spectrometry is widely used. In principle there are two scenarios. Proteins are pre-fractionated in some way, e.g. by gel electrophoresis or are analyzed as complex mixture (shot gun). Shot gun proteomics became recently more popular, because of te... |
Epigenetic-Mediated Downregulation of μ-Protocadherin in Colorectal Tumours
Bujko M, Kober P, Statkiewicz M, Mikula M, Ligaj M, Zwierzchowski L, Ostrowski J, Siedlecki JA
Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in ... |
