DNA methylation status predicts cell type-specific enhancer activity

Malgorzata Wiench, Suganthi John, S Baek, TA Johnson, MH Sung, T Escobar, CA Simmons, KH Pearce, SC Biddie, PJ Sabo, RE Thurman, JA Stamatoyannopoulos, GL Hager

Research output: Contribution to journalArticle

147 Citations (Scopus)


Cell-selective glucocorticoid receptor (GR) binding to distal regulatory elements is associated with cell type-specific regions of locally accessible chromatin. These regions can either pre-exist in chromatin (pre-programmed) or be induced by the receptor (de novo). Mechanisms that create and maintain these sites are not well understood. We observe a global enrichment of CpG density for pre-programmed elements, and implicate their demethylated state in the maintenance of open chromatin in a tissue-specific manner. In contrast, sites that are actively opened by GR (de novo) are characterized by low CpG density, and form a unique class of enhancers devoid of suppressive effect of agglomerated methyl-cytosines. Furthermore, treatment with glucocorticoids induces rapid changes in methylation levels at selected CpGs within de novo sites. Finally, we identify GR-binding elements with CpGs at critical positions, and show that methylation can affect GR-DNA interactions in vitro. The findings present a unique link between tissue-specific chromatin accessibility, DNA methylation and transcription factor binding and show that DNA methylation can be an integral component of gene regulation by nuclear receptors.
Original languageEnglish
Pages (from-to)3028-3039
Number of pages12
JournalThe EMBO journal
Issue number15
Publication statusPublished - 24 Jun 2011


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