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| 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
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| 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.
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| Overall design |
TRIM24 ChIP-seq with and without Estrogen (E2) in MCF7 human breast cancer-derived cell lines
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| Contributor(s) |
Jain A |
| Citation missing |
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| Submission date |
Apr 25, 2018 |
| Last update date |
Dec 03, 2019 |
| Contact name |
Jiejun Shi |
| E-mail(s) |
jiejuns@uci.edu
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| Organization name |
University of California Irvine
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| Department |
School of Medicine
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| Lab |
Li lab
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| Street address |
5270 California Ave
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| City |
Irvine |
| State/province |
CA |
| ZIP/Postal code |
92617 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA453537 |
| SRA |
SRP142605 |
