Gene Set: MALIK_REPRESSED_BY_ESTROGEN

Standard name MALIK_REPRESSED_BY_ESTROGEN
Systematic name M2470
Brief description Genes consistently and robustly repressed by estradiol [PubChem=5757] in MCF7 cells (breast cancer); this reperession was prevented by fulvestrant [PubChem=3478439].
Full description or abstract Activation of estrogen receptor alpha (ERalpha) results in both induction and repression of gene transcription; while mechanistic details of estrogen induction are well described, details of repression remain largely unknown. We characterized several ERalpha-repressed targets and examined in detail the mechanism for estrogen repression of Reprimo (RPRM), a cell cycle inhibitor. Estrogen repression of RPRM is rapid and robust and requires a tripartite interaction between ERalpha, histone deacetylase 7 (HDAC7), and FoxA1. HDAC7 is the critical HDAC needed for repression of RPRM; it can bind to ERalpha and represses ERalpha's transcriptional activity--this repression does not require HDAC7's deacetylase activity. We further show that the chromatin pioneer factor FoxA1, well known for its role in estrogen induction of genes, is recruited to the RPRM promoter, is necessary for repression of RPRM, and interacts with HDAC7. Like other FoxA1 recruitment sites, the RPRM promoter is characterized by H3K4me1/me2. Estrogen treatment causes decreases in H3K4me1/me2 and release of RNA polymerase II (Pol II) from the RPRM proximal promoter. Overall, these data implicate a novel role for HDAC7 and FoxA1 in estrogen repression of RPRM, a mechanism which could potentially be generalized to many more estrogen-repressed genes and hence be important in both normal physiology and pathological processes.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19917725   Authors: Malik S,Jiang S,Garee JP,Verdin E,Lee AV,O'Malley BW,Zhang M,Belaguli NS,Oesterreich S
Exact source Fig. 1A
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.1: First introduced

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