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Cell DOI:10.1016/j.cell.2006.02.041

A bivalent chromatin structure marks key developmental genes in embryonic stem cells.

Publication TypeJournal Article
Year of Publication2006
AuthorsBernstein, BE, Mikkelsen, TS, Xie, X, Kamal, M, Huebert, DJ, Cuff, J, Fry, B, Meissner, A, Wernig, M, Plath, K, Jaenisch, R, Wagschal, A, Feil, R, Schreiber, SL, Lander, ES
Date Published2006 Apr 21
KeywordsAnimals, Cell Differentiation, Cells, Cultured, Chromatin, DNA-Binding Proteins, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Developmental, Histones, Homeodomain Proteins, Male, Methylation, Mice, Mice, Inbred C57BL, Nanog Homeobox Protein, Nucleic Acid Conformation, Octamer Transcription Factor-3, Oligonucleotide Array Sequence Analysis, Stem Cells

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.


Alternate JournalCell
PubMed ID16630819
Grant ListCA84198 / CA / NCI NIH HHS / United States
GM38627 / GM / NIGMS NIH HHS / United States
HD045022 / HD / NICHD NIH HHS / United States