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A bivalent chromatin structure marks key developmental genes in embryonic stem cells, Cell 125 (2006)
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BibTeX
@MISC{Bernstein06abivalent,
author = {Bradley E. Bernstein and Tarjei S. Mikkelsen and Xiaohui Xie and Michael Kamal and Dana J. Huebert and James Cuff and Ben Fry and Alex Meissner and Marius Wernig and Kathrin Plath and Rudolf Jaenisch and Re Wagschal and Robert Feil and Stuart L. Schreiber and Eric S. L},
title = {A bivalent chromatin structure marks key developmental genes in embryonic stem cells, Cell 125},
year = {2006}
}
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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.
Keyphrases
key developmental gene bivalent chromatin structure embryonic stem cell e cell histone methylation novel chromatin-based mechanism bivalent domain mouse embryonic stem low level tf gene large region mammalian genome large hcne-rich locus important transcription factor specific modification pattern genome sequence conserved noncoding element hcne-rich region initial epigenetic landscape key regulatory control dna sequence differentiated cell silence developmental gene
