Journal ArticleDOI
A new world of Polycombs: unexpected partnerships and emerging functions.
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TLDR
The importance of these new PcG complexes for normal development and disease, their targeting mechanisms and their shifting roles in the course of differentiation are now the subject of investigation and the focus of this Review.Abstract:
Polycomb group (PcG) proteins are epigenetic repressors that are essential for the transcriptional control of cell differentiation and development. PcG-mediated repression is associated with specific post-translational histone modifications and is thought to involve both biochemical and physical modulation of chromatin structure. Recent advances show that PcG complexes comprise a multiplicity of variants and are far more biochemically diverse than previously thought. The importance of these new PcG complexes for normal development and disease, their targeting mechanisms and their shifting roles in the course of differentiation are now the subject of investigation and the focus of this Review.read more
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Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation
Neil P. Blackledge,Anca M. Farcas,Takashi Kondo,Hamish W King,Joanna F. McGouran,Lars L. P. Hanssen,Shinsuke Ito,Sarah Cooper,Kaori Kondo,Yoko Koseki,Tomoyuki Ishikura,Hannah K. Long,Thomas W. Sheahan,Neil Brockdorff,Benedikt M. Kessler,Haruhiko Koseki,Robert J. Klose +16 more
TL;DR: Using a de novo targeting assay in mouse embryonic stem cells, it is found that PRC1-dependent H2AK119ub1 leads to recruitment of PRC2 and H3K27me3 to effectively initiate a polycomb domain, providing a surprising PRC 1-dependent logic forPRC2 occupancy at target sites in vivo.
Journal ArticleDOI
Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide
TL;DR: The results show that it is the transcriptional state that governs PRC2 binding, and it is proposed that it binds by default to nontranscribed CGI genes to maintain their silenced state and to protect cell identity.
Journal ArticleDOI
Maintaining cell identity: PRC2-mediated regulation of transcription and cancer.
TL;DR: It is proposed that these apparently opposing roles of PRC2 in cancer are a consequence of the molecular function of the complex in maintaining, rather than specifying, the transcriptional repression state of its several thousand target genes.
Journal ArticleDOI
Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing
Angelo Amabile,Alessandro Migliara,Paola Capasso,Mauro Biffi,Davide Cittaro,Luigi Naldini,Angelo Lombardo +6 more
TL;DR: The endogenous retroviruses’ silencing machinery of embryonic stem cells is repurposed to stably silence three highly expressed genes in somatic cells by epigenetics, ensuring long-term memory of the repressive epigenetic state.
Journal ArticleDOI
Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies.
TL;DR: The clinical manifestations of CH, mechanisms contributing to its development, the role of CH in clonal evolution toward leukemia, and the contribution of CH to non-hematological disease states are discussed.
References
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Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
Rajnish A. Gupta,Nilay Shah,Kevin C. Wang,Jeewon Kim,Hugo M. Horlings,David J. Wong,Miao-Chih Tsai,Tiffany Hung,Pedram Argani,John L. Rinn,Yulei Wang,Pius Brzoska,Benjamin Kong,Rui-Chun Li,Robert B. West,Marc J. van de Vijver,Saraswati Sukumar,Howard Y. Chang +17 more
TL;DR: It is shown that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression, indicating that l incRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.
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
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
Ru Cao,Liangjun Wang,Hengbin Wang,Li Xia,Hediye Erdjument-Bromage,Paul Tempst,Richard S. Jones,Yi Zhang +7 more
TL;DR: The purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex, is reported, and it is demonstrated that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27).
Journal ArticleDOI
Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes
Miao-Chih Tsai,Ohad Manor,Yue Wan,Nima Mosammaparast,Jordon K. Wang,Fei Lan,Yang Shi,Eran Segal,Howard Y. Chang +8 more
TL;DR: The results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
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.