Record 5133   View: Standard Glossary  HistCite Guide
Author(s): Bernstein BE; Mikkelsen TS; Xie XH; Kamal M; Huebert DJ; Cuff J; Fry B; Meissner A; Wernig M; Plath K; Jaenisch R; Wagschal A; Feil R; Schreiber SL; Lander ES
Title: A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Source: CELL 125 (2): 315-326
Date: 2006 APR 21
Document Type: Journal : Article
DOI:  
Language: English
Comment:  
Address: Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA.
Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
Harvard Univ, Broad Inst, Cambridge, MA 02139 USA.
MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA.
CNRS, Inst Genet Mol, UMR 5535, Montpellier, France.
Univ Montpellier 2, Montpellier, France.
Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
Reprint: Bernstein, BE, Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA
02129 USA.
E-mail: bbernstein@partners.org
Author Keywords:  
KeyWords Plus: POLYCOMB GROUP-COMPLEXES; HISTONE CODE; HUMAN GENOME; TRANSPOSABLE ELEMENTS; EPIGENETIC REGULATION; X-INACTIVATION; METHYLATION; MOUSE; BINDING; METHYLTRANSFERASE
Abstract: The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed "bivalent domains," consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.
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