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

By Bradley E. Bernstein, Tarjei S. Mikkelsen, Xiaohui S. Xie, Michael Kamal, Dana J. Huebert, James A. Cuff, B. Fry, Alexander Meissner, Marius Wernig, Kathrin Plath and 5 more. Cell, 2006

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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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/05a987490ffb31b16a4d850b11a267e47c71a963

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Citations in the corpus

How is pluripotency determined and maintained? (2007, background): “However, Bernstein et al. reported that in mouse ES cells, these histone marks co-localize in particular regions, which they named ‘bivalent domains’ (Bernstein et al., 2006).”
Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. (2007, background): “Among PcG proteins, PRC2 is of particular importance since it has been linked to stem cell biology and cancer (Kleer et al. 2003; Gil et al. 2005; Bernstein et al. 2006; Boyer et al. 2006; Bracken et al. 2006; Holden 2006; Kalantry et al. 2006; Kamminga et al. 2006; Lee et al. 2006).”
Eukaryotic core promoters and the functional basis of transcription initiation (2018, neutral): “gene core promoters, which in embryonic stem cells, however, are distinctly bivalently marked with both H3K4me3 and the repressive chromatin modification H3K27me3 (reF.(236); see the figure, part c).”
Epigenetic Determinants of Cancer. (2016, background): “7B) (Bernstein et al. 2006; Chi and Bernstein 2009; Baylin and Jones 2011; Shen and Laird 2013).”
Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, neutral): “, 2011), as well as bivalent domains,which containH3K4me3 (active histone mark) and H3K27me3 (polycomb repression complex 2 [PRC2]deposited repressive mark) (Bernstein et al., 2006).”
Systematic mapping of occluded genes by cell fusion reveals prevalence and stability of cis-mediated silencing in somatic cells (2014, background): “It has been reported that mouse ESCs possess many ‘‘bivalent’’ domains where the active mark H3K4m3 and the silent mark H3K27me3 coexist (Bernstein et al. 2006).”
High-resolution profiling of histone methylations in the human genome. (2007, background): “The bivalent domains, where H3K4me3 and H3K27me3 signals exist next to each other, are suggested to play regulatory roles for the differentiation of embryonic stem cells (Bernstein et al., 2006).”