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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The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer
Xianqing Mao,Caroline Gauche,Michael W.H. Coughtrie,Michael W.H. Coughtrie,Catherine Bui,Sandrine Gulberti,F. Merhi-Soussi,Nick Ramalanjaona,Isabelle Bertin-Jung,A. Diot,D. Dumas,N. de Freitas Caires,A. M. Thompson,J-C Bourdon,Mohamed Ouzzine,Sylvie Fournel-Gigleux +15 more
TL;DR: 3-OST3A is defined as a novel regulator of breast cancer pathogenicity, displaying tumor-suppressive or oncogenic activities in a cell- and tumor-dependent context, and the clinical value of the HS-O-sulfotransferase 3-OST 3A as a prognostic marker in HER2+ patients is demonstrated.
Journal ArticleDOI
SAR of amino pyrrolidines as potent and novel protein-protein interaction inhibitors of the PRC2 complex through EED binding.
Michael L. Curtin,Marina A. Pliushchev,Huan-Qiu Li,Maricel Torrent,Justin D. Dietrich,Clarissa G. Jakob,Haizhong Zhu,Hongyu Zhao,Ying Wang,Zhiqin Ji,Richard F. Clark,Kathy Sarris,Sujatha Selvaraju,Bailin Shaw,Mikkel Algire,Yupeng He,Paul L. Richardson,Ramzi F. Sweis,Chaohong Sun,Gary G. Chiang,Michael R. Michaelides +20 more
TL;DR: SAR studies of a series of dimethylamino pyrrolidines reported as novel inhibitors of the PRC2 complex through disruption of EED/H3K27me3 binding culminated in the identification of compound 2, the authors' nanomolar proof-of-concept (PoC) inhibitor which provided on-target tumor growth inhibition in a mouse xenograft model.
Journal ArticleDOI
EZH2-Mediated Epigenetic Suppression of GDF15 Predicts a Poor Prognosis and Regulates Cell Proliferation in Non-Small-Cell Lung Cancer
Xiyi Lu,Xuezhi He,Jun Su,Jing Wang,Xinyin Liu,Kun Xu,Wei De,Erbao Zhang,Renhua Guo,Yuenian Eric Shi +9 more
TL;DR: The data uncover that GDF15 is a direct target of EZH2 and, as a regulator of proliferation, might serve as a candidate prognostic biomarker and target for new therapies in human NSCLC.
Journal ArticleDOI
A Tale of Two Cities: How Xist and its partners localize to and silence the bicompartmental X.
TL;DR: This review summarizes and integrates findings on XCI findings with a particular focus on the redundant yet mutually reinforcing pathways that enable long-term transcriptional repression throughout the soma, including an exploration of concurrent epigenetic changes acting in parallel within two distinct compartments of the inactive X.
Journal ArticleDOI
The persistent organochlorine pesticide endosulfan modulates multiple epigenetic regulators with oncogenic potential in MCF-7 cells.
TL;DR: Modulatory impact of α-endosulfan on multiple cellular epigenetic regulators, known to possess oncogenic potential, might contribute to mechanistic insight of its action in future.
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.