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Series GSE113654 Query DataSets for GSE113654
Status Public on Dec 01, 2019
Title Cyclic LSD1 recruitment and dynamic H3K4 methylation establish TRIM24-activated estrogen response
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The role of histone lysine methylation in estrogen receptor-alpha (ERα)-activated transcription is highly context-specific and poorly understood. Here, we show that lysine demethylase 1 (LSD1) mediates loss of H3 lysine 4 dimethylation (H3K4me2) in coordination with tripartite-motif-containing protein 24 (TRIM24)- regulated growth of breaset cancer-derived cells. We performed global profiling of histone H3K4me2 in comparison to genome-wide binding of TRIM24 in MCF7 cells when estrogen is depleted or added. We found specific subsets of genes with functions in transcription and cell proliferation are depleted of H3K4me2 at TRIM24 binding sites. Chromatin immunoprecipitation (ChIP) analyses over a time course of estrogen induction revealed cyclic demethylation of H3K4me2, LSD1, TRIM24 and ERα binding. Inhibition of LSD1 enzymatic activity led to increased H3K4me2 and decreased estrogen response of TRIM24-dependent genes. Additon of a small molecule inhibitor of the TRIM24 bromodomain or depletion of TRIM24 expression amplified the impact of LSD1 inhbition as measured by survival and proliferation of MCF7 cells, suggesting that combinatorial inhibition of LSD1 and TRIM24 may be effective in targeting ER-positive breast cancers.
Overall design TRIM24 ChIP-seq with and without Estrogen (E2) in MCF7 human breast cancer-derived cell lines
Contributor(s) Jain A
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Submission date Apr 25, 2018
Last update date Dec 03, 2019
Contact name Jiejun Shi
Organization name University of California Irvine
Department School of Medicine
Lab Li lab
Street address 5270 California Ave
City Irvine
State/province CA
ZIP/Postal code 92617
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (3)
GSM3110727 TRIM24 ChIP-seq in E2pos
GSM3110728 TRIM24 ChIP-seq in E2neg
GSM3110729 MCF7 Input
BioProject PRJNA453537
SRA SRP142605

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Supplementary file Size Download File type/resource
GSE113654_RAW.tar 690.6 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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