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Series GSE74238 Query DataSets for GSE74238
Status Public on Apr 15, 2016
Title BRD4 connects enhancer remodeling to senescence immune surveillance (ChIP-Seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Cellular senescence is a homeostatic program associated with tumor suppression, wound healing, and certain age related pathologies. Senescent cells display a repressive chromatin configuration thought to stably silence proliferation-promoting genes, while at the same time activate 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 inhibition disrupts immune cell-mediated targeting and elimination of premalignant senescent cells in vitro and in vivo. Our results identify a critical role for BRD4-bound super-enhancers in senescence immune surveillance and in the proper execution of a tumor-suppressive program.
 
Overall design Chip-seq for H3K27Ac and BRD4 in proliferating, quiescent or senescent (HrasV12) human fibroblasts (IMR90)
 
Contributor(s) Roe J, Tasdemir N, Banito A, Alonso-Curbelo D, Lowe S
Citation(s) 27099234
Submission date Oct 21, 2015
Last update date May 15, 2019
Contact name Jae Seok Roe
E-mail(s) jroe@yonsei.ac.kr
Organization name Yonsei University
Street address Yonsei-ro, 50
City Seoul
ZIP/Postal code 03722
Country South Korea
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (22)
GSM1915113 H3K27Ac ChIP-Seq_Proliferating IMR90
GSM1915114 H3K27Ac ChIP-Seq_Quiescent IMR90
GSM1915115 H3K27Ac ChIP-Seq_Senescent IMR90
This SubSeries is part of SuperSeries:
GSE74328 BRD4 connects enhancer remodeling to senescence immune surveillance
Relations
BioProject PRJNA299593
SRA SRP065195

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Supplementary file Size Download File type/resource
GSE74238_RAW.tar 3.5 Gb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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