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.
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E.; Mikkelsen, T. S.; Xie, X. H.; Kamal, M.; Huebert, D. J.; Cuff, J.; Fry, B.; Meissner, A.; Wernig, M.; Plath, K.; Jaenisch, R.; Wagschal, A.; Feil, R.; Schreiber, S. L.; Lander, E. S.
2006-04-21 / vol 125 / pages 315-326
IGMM team(s) involved in this publication
Genomic Imprinting and Development
mouse; x-inactivation; methylation; methyltransferase; binding; human genome; epigenetic regulation; histone code; polycomb group-complexes; transposable elements