NF-kB coordinates rapid, BRD4-dependent remodeling of proinflammatory super-enhancers [Chem-Seq]

ABSTRACT: Proinflammatory stimuli rapidly and globally remodel chromatin landscape, thereby enabling transcriptional responses. Yet, the mechanisms coupling chromatin regulators to the master regulatory inflammatory transcription factor NF-kB remain poorly understood.  We report in human endothelial cells (ECs) that activated NF-kB binds to enhancers, provoking a rapid, global redistribution of BRD4 preferentially at super-enhancers, large enhancer domains highly bound by chromatin regulators.  Newly established NF-kB super-enhancers drive nearby canonical inflammatory response genes. In both ECs and macrophages BET bromodomain inhibition prevents super-enhancer formation downstream of NF-kB activation, abrogating proinflammatory transcription. In TNFa-activated endothelium this culminates in functi

ORGANISM(S): Homo sapiens

SUBMITTER: James Bradner 

PROVIDER: E-GEOD-60051 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress