Journal article

BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance.

Nilgun Tasdemir, Ana Banito, Jae-Seok Roe, Direna Alonso-Curbelo, Matthew Camiolo, Darjus F Tschaharganeh, Chun-Hao Huang, Ozlem Aksoy, Jessica E Bolden, Chi-Chao Chen, Myles Fennell, Vishal Thapar, Agustin Chicas, Christopher R Vakoc, Scott W Lowe

Cancer Discov | Published : 2016

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 ..

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University of Melbourne Researchers