Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding

SC Biddie, S John, PJ Sabo, RE Thurman, RL Schiltz, TA Johnson, MH Sung, S Trump, SL Lightman, C Vinson, JA Stamatoyannopoulos, GL Hager

Research output: Contribution to journalArticle (Academic Journal)

272 Citations (Scopus)

Abstract

Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor (GR) is mediated by interactions with coregulators. The role of these interactions in determining selective binding of GR to regulatory elements remains unclear. Recent findings indicate that a large fraction of genomic GR binding coincides with chromatin that is accessible prior to hormone treatment, suggesting that receptor binding is dictated by proteins that maintain chromatin in an open state. Combining DNaseI accessibility and chromatin immunoprecipitation with high-throughput sequencing, we identify the activator protein 1 (AP1) as a major partner for productive GR-chromatin interactions. AP1 is critical for GR-regulated transcription and recruitment to co-occupied regulatory elements, illustrating an extensive AP1-GR interaction network. Importantly, the maintenance of baseline chromatin accessibility facilitates GR recruitment and is dependent on AP1 binding. We propose a model in which the basal occupancy of transcription factors acts to prime chromatin and direct inducible transcription factors to select regions in the genome.
Translated title of the contributionTranscription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding
Original languageEnglish
Pages (from-to)145 - 155
Number of pages11
JournalMolecular Cell
Volume43
Issue number1
DOIs
Publication statusPublished - 8 Jul 2011

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