BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance.

ABSTRACT:

Unlabelled

Oncogene-induced senescence is a potent barrier to tumorigenesis that limits cellular expansion following certain oncogenic events. Senescent cells display a repressive chromatin configuration thought to stably silence proliferation-promoting genes while simultaneously activating an unusual form of immune surveillance involving a secretory program referred to as the senescence-associated secretory phenotype (SASP). Here, we demonstrate that senescence also involves a global remodeling of the enhancer landscape with recruitment of the chromatin reader BRD4 to newly activated super-enhancers adjacent to key SASP genes. Transcriptional profiling and functional studies indicate that BRD4 is required for the SASP and downstream paracrine signaling. Consequently, BRD4 inhibiti

SUBMITTER: Tasdemir N 

PROVIDER: S-EPMC4893996 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature