Scientific Publications

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

Publication TypeJournal Article
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, and Lander E. S.
AbstractThe 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.
Year of Publication2006
JournalCell
Volume125
Issue2
Pages315-26
Date Published (YYYY/MM/DD)2006/04/21
ISSN Number0092-8674
DOI10.1016/j.cell.2006.02.041
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/16630819?dopt=Abstract