Journal ArticleDOI
Transcriptional regulation by Polycomb group proteins.
TLDR
The current knowledge of the PRC complexes is discussed, how they are targeted to chromatin and how the high diversity of the PcG proteins allows these complexes to influence cell identity.Abstract:
Polycomb group (PcG) proteins function within Polycomb repressive complexes (PRCs), which modify histones and other proteins and silence target genes. This Review highlights new insights into the role of PcG proteins in gene regulation, specifically in controlling self-renewal and differentiation of embryonic stem cells, and into how PRCs are targeted to chromatin.read more
Citations
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Journal ArticleDOI
Dysregulation of iron homeostasis by TfR-1 renders EZH2 wild type diffuse large B-cell lymphoma resistance to EZH2 inhibition.
Ya-fang Wang,Jiang Xiao,Qianqian Shen,Shuaishuai Chi,Yinglei Gao,Dong-ze Lin,Jian Ding,Yanfen Fang,Yi Chen +8 more
Posted ContentDOI
Phenotypic pliancy and the breakdown of epigenetic polycomb mechanisms
TL;DR: An abstract computational model is developed to study the emergence of phenotypic pliancy from a general systems-level view and confirms the hypothesis over a wide range of simulated gene-regulatory networks and Polycomb mechanisms’ patterns that such behavior can be caused by dysregulation of polycomb mechanisms.
Journal ArticleDOI
Putting the brakes on transcription at damaged chromatin: Do Polycomb silencers do more than modify histones?
TL;DR: A new mode of BMI1-mediated transcription arrest at lesions that involves UBR5 E3 ligase and FACT histone chaperon is described.
Book ChapterDOI
Pharmacoepigenetics of EZH2 Inhibitors
TL;DR: The regulation of EZH2, PRC2-mediated EZh2 targets, EzH2 targets outsidePRC2, common EZ h2 mutations, viral interactions of Ezh2, and EZ H2 inhibitors are described.
Posted ContentDOI
Select EZH2 inhibitors enhance the viral mimicry effects of DNMT inhibition through a mechanism involving calcium-calcineurin-NFAT signaling
Alison A. Chomiak,Rochelle L. Tiedemann,Yanqing Liu,Xiangqian Kong,Evan M. Cornett,Michael J. Topper,Stephen B. Baylin,Scott B. Rothbart +7 more
TL;DR: In this article , the authors show that low-dose DNMT inhibition sensitizes cells to selective EZH2 inhibitors that have limited single agent toxicity, and that EZh2 inhibition enhances DNMT inhibitor-driven molecular and therapeutic effects.
References
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Journal ArticleDOI
Crystal structure of the nucleosome core particle at 2.8 Å resolution
TL;DR: The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it.
Journal ArticleDOI
High-resolution profiling of histone methylations in the human genome.
Artem Barski,Suresh Cuddapah,Kairong Cui,Tae-Young Roh,Dustin E. Schones,Zhibin Wang,Gang Wei,Iouri Chepelev,Keji Zhao +8 more
TL;DR: High-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF across the human genome using the Solexa 1G sequencing technology are generated.
Journal ArticleDOI
Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs
John L. Rinn,Michael Kertesz,Jordon K. Wang,Sharon L. Squazzo,Xiao Xu,Samantha A. Brugmann,L. Henry Goodnough,Jill A. Helms,Peggy J. Farnham,Eran Segal,Howard Y. Chang +10 more
TL;DR: The transcriptional landscape of the four human HOX loci is characterized at five base pair resolution in 11 anatomic sites and 231 HOX ncRNAs are identified that extend known transcribed regions by more than 30 kilobases, suggesting transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance.
Journal ArticleDOI
A gene complex controlling segmentation in Drosophila.
TL;DR: The wild-type and mutant segmentation patterns are consistent with an antero-posterior gradient in repressor concentration along the embryo and a proximo-distal gradient along the chromosome in the affinities for repressor of each gene's cis-regulatory element.
Journal ArticleDOI
Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression
Ahmad M. Khalil,Mitchell Guttman,Maite Huarte,Manuel Garber,Arjun Raj,Dianali Rivea Morales,Kelly Thomas,Aviva Presser,Bradley E. Bernstein,Alexander van Oudenaarden,Aviv Regev,Eric S. Lander,John L. Rinn +12 more
TL;DR: A model in which some lincRNAs guide chromatin-modifying complexes to specific genomic loci to regulate gene expression is proposed, and it is shown that siRNA-mediated depletion of certain linc RNAs associated with PRC2 leads to changes in gene expression.