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Series GSE65886 Query DataSets for GSE65886
Status Public on May 02, 2015
Title H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Hormone-dependent gene expression requires dynamic and coordinated epigenetic changes. Estrogen receptor-positive (ER+) breast cancer is particularly dependent upon extensive chromatin remodeling and changes in histone modifications for the induction of hormone-responsive gene expression. Our previous studies established an important role of bromodomain-containing protein-4 (BRD4) in promoting estrogen-regulated transcription and proliferation of ER+ breast cancer cells. Here, we investigated the association between genome-wide occupancy of histone H4 acetylation at lysine 12 (H4K12ac) and BRD4 in the context of estrogen-induced transcription. Similar to BRD4, we observed that H4K12ac occupancy increases near the transcription start sites (TSS) of estrogen-induced genes as well as at distal ERα binding sites in an estrogen-dependent manner. Interestingly, H4K12ac occupancy highly correlates with BRD4 binding and enhancer RNA production on ERα-positive enhancers. Consistent with an importance in estrogen-induced gene transcription, H4K12ac occupancy globally increased in ER-positive cells relative to ER-negative cells and these levels were further increased by estrogen treatment in an ERα-dependent manner. Together, these findings reveal a strong correlation between H4K12ac and BRD4 occupancy with estrogen-dependent gene transcription and further suggest that modulators of H4K12ac and BRD4 may serve as new therapeutic targets for hormone-dependent cancers.
Overall design ChIP-seq profiles of H4K12ac in MCF7 cells treated with +/- estrogen treatment and MCF10A cells.
Contributor(s) Nagarajan S, Johnsen SA
Citation(s) 25788266
Submission date Feb 12, 2015
Last update date May 15, 2019
Contact name Steven A Johnsen
Organization name University Medical Center Göttingen
Department Department of General, Visceral and Pediatric Surgery
Street address Robert-Koch-Straße 40
City Göttingen
State/province Niedersachsen
ZIP/Postal code 37075
Country Germany
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (8)
GSM1608297 MCF7 Veh rep1
GSM1608298 MCF7 Veh rep2
GSM1608299 MCF7 E2 rep1
BioProject PRJNA275306
SRA SRP054970

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Supplementary file Size Download File type/resource
GSE65886_MCF10A_H4K12ac.bigwig.gz 304.1 Mb (ftp)(http) BIGWIG
GSE65886_MCF7_H4K12ac_E2.bigwig.gz 229.9 Mb (ftp)(http) BIGWIG
GSE65886_MCF7_H4K12ac_Veh.bigwig.gz 247.8 Mb (ftp)(http) BIGWIG
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