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https://www.readbyqxmd.com/read/28933651/characterization-of-h3-3k36m-as-a-tool-to-study-h3k36-methylation-in-cancer-cells
#1
Saumya M Sankaran, Or Gozani
Recurrent mutations at key lysine residues in the histone variant H3.3 are thought to play an etiologic role in the development of distinct subsets of pediatric gliomas and bone and cartilage cancers. H3.3K36M is one such mutation that was originally identified in chondroblastomas, and its expression in these tumors contributes to oncogenic reprogramming by triggering global depletion of dimethylation and trimethylation at H3K36 with a concomitant increase in the levels of H3K27 trimethylation. H3.3K36M expression can also cause epigenomic changes in cell types beyond chondrocytic cells...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28900200/differential-landscape-of-non-cpg-methylation-in-embryonic-stem-cells-and-neurons-caused-by-dnmt3s
#2
Jong-Hun Lee, Sung-Joon Park, Kenta Nakai
Methylated non-CpGs (mCpH; H means A, C, and T) have emerged as key epigenetic marks in mammalian embryonic stem cells (ESCs) and neurons, regulating cell type-specific functions. In these two cell types, mCpHs show distinct motifs and correlations to transcription that could be a key in understanding the cell type-specific regulations. Thus, we attempted to uncover the underlying mechanism of the differences in ESCs and neurons by conducting a comprehensive analysis of public whole genome bisulfite sequencing data...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28869966/polycomb-like-proteins-link-the-prc2-complex-to-cpg-islands
#3
Haojie Li, Robert Liefke, Junyi Jiang, Jesse Vigoda Kurland, Wei Tian, Pujuan Deng, Weidi Zhang, Qian He, Dinshaw J Patel, Martha L Bulyk, Yang Shi, Zhanxin Wang
The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form sub-complexes with PRC2 core components, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation...
September 14, 2017: Nature
https://www.readbyqxmd.com/read/28854740/the-atp-dependent-chromatin-remodeler-chd1-is-recruited-by-transcription-elongation-factors-and-maintains-h3k4me3-h3k36me3-domains-at-actively-transcribed-and-spliced-genes
#4
Yaelim Lee, Daechan Park, Vishwanath R Iyer
No abstract text is available yet for this article.
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28835804/design-of-kdm4-inhibitors-with-antiproliferative-effects-in-cancer-models
#5
Young K Chen, Tiziana Bonaldi, Alessandro Cuomo, Joselyn R Del Rosario, David J Hosfield, Toufike Kanouni, Shih-Chu Kao, Chon Lai, Neethan A Lobo, Jennifer Matuszkiewicz, Andrew McGeehan, Shawn M O'Connell, Lihong Shi, Jeffrey A Stafford, Ryan K Stansfield, James M Veal, Michael S Weiss, Natalie Y Yuen, Michael B Wallace
Histone lysine demethylases (KDMs) play a vital role in the regulation of chromatin-related processes. Herein, we describe our discovery of a series of potent KDM4 inhibitors that are both cell permeable and antiproliferative in cancer models. The modulation of histone H3K9me3 and H3K36me3 upon compound treatment was verified by homogeneous time-resolved fluorescence assay and by mass spectroscopy detection. Optimization of the series using structure-based drug design led to compound 6 (QC6352), a potent KDM4 family inhibitor that is efficacious in breast and colon cancer PDX models...
August 10, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28820292/p53-binding-sites-in-normal-and-cancer-cells-are-characterized-by-distinct-chromatin-context
#6
Feifei Bao, Peter R LoVerso, Jeffrey N Fisk, Victor B Zhurkin, Feng Cui
The tumor suppressor protein p53 interacts with DNA in a sequence-dependent manner. Thousands of p53 binding sites have been mapped genome-wide in normal and cancer cells. However, the way p53 selectively binds its cognate sites in different types of cells is not fully understood. Here, we performed a comprehensive analysis of 25 published p53 cistromes and identified 3,551 and 6,039 'high-confidence' binding sites in normal and cancer cells, respectively. Our analysis revealed two distinct epigenetic features underlying p53-DNA interactions in vivo...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28808080/characterization-of-the-human-thyroid-epigenome
#7
Celia Siu, Sam Michael Wiseman, Sitanshu Gakkhar, Alireza Heravi-Moussavi, Misha Bilenky, Annaick Carles, Thomas Sierocinski, Angela Tam, Eric Yang Zhao, Katayoon Kasaian, Richard A Moore, Andrew J Mungall, Blair Walker, Thomas Thomson, Marco A Marra, Martin Hirst, Steven Jones
The thyroid gland, necessary for normal human growth and development, functions as an essential regulator of metabolism by the production and secretion of appropriate levels of thyroid hormone. However, assessment of abnormal thyroid function may be challenging suggesting a more fundamental understanding of normal function is needed. One way to characterize normal gland function is to study the epigenome and resulting transcriptome within its constituent cells. This study generates the first published reference epigenomes for human thyroid from four individuals using ChIP-seq and RNA-seq...
August 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28808051/error-prone-dna-repair-targets-the-h3k36me3-chromatin-of-active-genes
#8
(no author information available yet)
Carcinogen-associated error-prone DNA repair increases the mutation rate of active genes in cancer.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28790329/kdm4b-mediated-reduction-of-h3k9me3-and-h3k36me3-levels-improves-somatic-cell-reprogramming-into-pluripotency
#9
Jingwei Wei, Jisha Antony, Fanli Meng, Paul MacLean, Rebekah Rhind, Götz Laible, Björn Oback
Correct reprogramming of epigenetic marks is essential for somatic cells to regain pluripotency. Repressive histone (H) lysine (K) methylation marks are known to be stable and difficult to reprogram. In this study, we generated transgenic mice and mouse embryonic fibroblasts (MEFs) for the inducible expression of KDM4B, a demethylase that removes H3 K9 and H3K36 trimethylation (me3) marks (H3K9/36me3). Upon inducing Kdm4b, H3K9/36me3 levels significantly decreased compared to non-induced controls. Concurrently, H3K9me1 levels significantly increased, while H3K9me2 and H3K27me3 remained unchanged...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768201/human-tfiih-kinase-cdk7-regulates-transcription-associated-chromatin-modifications
#10
Christopher C Ebmeier, Benjamin Erickson, Benjamin L Allen, Mary A Allen, Hyunmin Kim, Nova Fong, Jeremy R Jacobsen, Kaiwei Liang, Ali Shilatifard, Robin D Dowell, William M Old, David L Bentley, Dylan J Taatjes
CDK7 phosphorylates the RNA polymerase II (pol II) C-terminal domain CTD and activates the P-TEFb-associated kinase CDK9, but its regulatory roles remain obscure. Here, using human CDK7 analog-sensitive (CDK7as) cells, we observed reduced capping enzyme recruitment, increased pol II promoter-proximal pausing, and defective termination at gene 3' ends upon CDK7 inhibition. We also noted that CDK7 regulates chromatin modifications downstream of transcription start sites. H3K4me3 spreading was restricted at gene 5' ends and H3K36me3 was displaced toward gene 3' ends in CDK7as cells...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28753428/clustered-mutation-signatures-reveal-that-error-prone-dna-repair-targets-mutations-to-active-genes
#11
Fran Supek, Ben Lehner
Many processes can cause the same nucleotide change in a genome, making the identification of the mechanisms causing mutations a difficult challenge. Here, we show that clustered mutations provide a more precise fingerprint of mutagenic processes. Of nine clustered mutation signatures identified from >1,000 tumor genomes, three relate to variable APOBEC activity and three are associated with tobacco smoking. An additional signature matches the spectrum of translesion DNA polymerase eta (POLH). In lymphoid cells, these mutations target promoters, consistent with AID-initiated somatic hypermutation...
July 27, 2017: Cell
https://www.readbyqxmd.com/read/28706445/histone-demethylase-kdm2b-upregulates-histone-methyltransferase-ezh2-expression-and-contributes-to-the-progression-of-ovarian-cancer-in-vitro-and-in-vivo
#12
Yan Kuang, Fangfang Lu, Jianfeng Guo, Hong Xu, Qi Wang, Chaohuan Xu, Longjia Zeng, Suyi Yi
Aberrant histone methylation contributes to the progression and development of many tumors. Histone methylation is a dynamic process regulated by both histone demethylase and histone methyltransferase, which ultimately alters the levels of gene transcription. However, the relationship between histone demethylase and histone methyltransferase, as well as their regulatory mechanisms in ovarian cancer development, is still unclear. Lysine-specific demethylase 2B (KDM2B) is a key demethylase of H3K36me3 and H3K4me3 that regulates gene expression and plays a role in tumorigenesis via epigenetic mechanisms...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28678539/histone-3-modifications-and-blood-pressure-in-the-beijing-truck-driver-air-pollution-study
#13
Jacob K Kresovich, Zhou Zhang, Fang Fang, Yinan Zheng, Marco Sanchez-Guerra, Brian T Joyce, Jia Zhong, Yana Chervona, Sheng Wang, Dou Chang, John P McCracken, Anaite Díaz, Matteo Bonzini, Michele Carugno, Petros Koutrakis, Choong-Min Kang, Shurui Bian, Tao Gao, Hyang-Min Byun, Joel Schwartz, Andrea A Baccarelli, Lifang Hou
CONTEXT: Histone modifications regulate gene expression; dysregulation has been linked with cardiovascular diseases. Associations between histone modification levels and blood pressure in humans are unclear. OBJECTIVE: We examine the relationship between global histone concentrations and various markers of blood pressure. MATERIALS AND METHODS: Using the Beijing Truck Driver Air Pollution Study, we investigated global peripheral white blood cell histone modifications (H3K9ac, H3K9me3, H3K27me3, and H3K36me3) associations with pre- and post-work measurements of systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP), and pulse pressure (PP) using multivariable mixed-effect models...
September 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/28673974/mrg15-mediated-tethering-of-palb2-to-unperturbed-chromatin-protects-active-genes-from-genotoxic-stress
#14
Jean-Yves Bleuyard, Marjorie Fournier, Ryuichiro Nakato, Anthony M Couturier, Yuki Katou, Christine Ralf, Svenja S Hester, Daniel Dominguez, Daniela Rhodes, Timothy C Humphrey, Katsuhiko Shirahige, Fumiko Esashi
The partner and localiser of BRCA2 (PALB2) plays important roles in the maintenance of genome integrity and protection against cancer. Although PALB2 is commonly described as a repair factor recruited to sites of DNA breaks, recent studies provide evidence that PALB2 also associates with unperturbed chromatin. Here, we investigated the previously poorly described role of chromatin-associated PALB2 in undamaged cells. We found that PALB2 associates with active genes through its major binding partner, MRG15, which recognizes histone H3 trimethylated at lysine 36 (H3K36me3) by the SETD2 methyltransferase...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28654864/wolf-hirschhorn-syndrome-candidate-1-whsc1-functions-as-a-tumor-suppressor-by-governing-cell-differentiation
#15
Chuan Yu, Xiaomin Yao, Linjie Zhao, Ping Wang, Qian Zhang, Chengjian Zhao, Shaohua Yao, Yuquan Wei
Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a histone 3 lysine 36 (H3K36) specific methyltransferase that is frequently deleted in Wolf-Hirschhorn syndrome (WHS). Whsc1 is also found mutated in a subgroup of B-cell derived malignant diseases by genomic translocation or point mutation, both of which resulted in hyperactivity of WHSC1 mediated H3K36 methylation and uncontrolled cell proliferation, suggesting that whsc1 functions as an oncogene. However, here we provided evidences to show that whsc1 also has tumor suppressor functions...
June 24, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28648780/the-histone-acetyltransferase-mst2-protects-active-chromatin-from-epigenetic-silencing-by-acetylating-the-ubiquitin-ligase-brl1
#16
Valentin Flury, Paula Raluca Georgescu, Vytautas Iesmantavicius, Yukiko Shimada, Tahsin Kuzdere, Sigurd Braun, Marc Bühler
Faithful propagation of functionally distinct chromatin states is crucial for maintaining cellular identity, and its breakdown can lead to diseases such as cancer. Whereas mechanisms that sustain repressed states have been intensely studied, regulatory circuits that protect active chromatin from inactivating signals are not well understood. Here we report a positive feedback loop that preserves the transcription-competent state of RNA polymerase II-transcribed genes. We found that Pdp3 recruits the histone acetyltransferase Mst2 to H3K36me3-marked chromatin...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28629467/chromatin-marks-and-ambient-temperature-dependent-flowering-strike-up-a-novel-liaison
#17
Alexander Steffen, Dorothee Staiger
A distinct chromatin mark, H3K36me3, has been found to engage in temperature-dependent alternative splicing and ambient temperature-dependent flowering-time control in Arabidopsis.
June 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28609483/histone-posttranslational-modifications-predict-specific-alternative-exon-subtypes-in-mammalian-brain
#18
Qiwen Hu, Eun Ji Kim, Jian Feng, Gregory R Grant, Elizabeth A Heller
A compelling body of literature, based on next generation chromatin immunoprecipitation and RNA sequencing of reward brain regions indicates that the regulation of the epigenetic landscape likely underlies chronic drug abuse and addiction. It is now critical to develop highly innovative computational strategies to reveal the relevant regulatory transcriptional mechanisms that may underlie neuropsychiatric disease. We have analyzed chromatin regulation of alternative splicing, which is implicated in cocaine exposure in mice...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28566089/histone-h3-lysine-36-methylation-affects-temperature-induced-alternative-splicing-and-flowering-in-plants
#19
A Pajoro, E Severing, G C Angenent, R G H Immink
BACKGROUND: Global warming severely affects flowering time and reproductive success of plants. Alternative splicing of pre-messenger RNA (mRNA) is an important mechanism underlying ambient temperature-controlled responses in plants, yet its regulation is poorly understood. An increase in temperature promotes changes in plant morphology as well as the transition from the vegetative to the reproductive phase in Arabidopsis thaliana via changes in splicing of key regulatory genes. Here we investigate whether a particular histone modification affects ambient temperature-induced alternative splicing and flowering time...
June 1, 2017: Genome Biology
https://www.readbyqxmd.com/read/28546430/cross-talk-between-the-h3k36me3-and-h4k16ac-histone-epigenetic-marks-in-dna-double-strand-break-repair
#20
COMPARATIVE STUDY
Lin Li, Yinsheng Wang
Post-translational modifications of histone proteins regulate numerous cellular processes. Among these modifications, trimethylation of lysine 36 in histone H3 (H3K36me3) and acetylation of lysine 16 in histone H4 (H4K16ac) have important roles in transcriptional regulation and DNA damage response signaling. However, whether these two epigenetic histone marks are mechanistically linked remains unclear. Here we discovered a new pathway through which H3K36me3 stimulates H4K16ac upon DNA double-strand break (DSB) induction in human cells...
July 14, 2017: Journal of Biological Chemistry
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