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Cohesin is required for expression of the estrogen receptor-alpha (ESR1) gene

ABSTRACT: In this study we show that depletion of the cohesin subunit SMC3 or the Mediator subunit MED12 significantly impairs the ERα-regulated transcriptome. Surprisingly, SMC3 depletion appears to elicit this effect indirectly by rapidly decreasing ESR1 transcription and ERα protein levels. Moreover, we provide evidence that both SMC3 and MED12 colocalize on the ESR1 gene and are mutually required for occupancy as well as for transcriptional elongation. Finally, we show that extended proteasome inhibition decreases the mRNA expression of cohesin subunits which accompanies a decrease in ESR1 mRNA and ERα protein levels as well as estrogen-regulated transcription. Conclusions: These results identify the ESR1 gene as a cohesin/Mediator-dependent gene and indicate that this regulation may potentially be exploited for the treatment of estrogen-dependent breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE38252 | GEO | 2013/05/20

SECONDARY ACCESSION(S): PRJNA167524

REPOSITORIES: GEO

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Cohesin is required for expression of the estrogen receptor-alpha (ESR1) gene

Project description:In this study we show that depletion of the cohesin subunit SMC3 or the Mediator subunit MED12 significantly impairs the ERα-regulated transcriptome. Surprisingly, SMC3 depletion appears to elicit this effect indirectly by rapidly decreasing ESR1 transcription and ERα protein levels. Moreover, we provide evidence that both SMC3 and MED12 colocalize on the ESR1 gene and are mutually required for occupancy as well as for transcriptional elongation. Finally, we show that extended proteasome inhibition decreases the mRNA expression of cohesin subunits which accompanies a decrease in ESR1 mRNA and ERα protein levels as well as estrogen-regulated transcription. Conclusions: These results identify the ESR1 gene as a cohesin/Mediator-dependent gene and indicate that this regulation may potentially be exploited for the treatment of estrogen-dependent breast cancer. This set contains 18 microarray samples with triplicates for each condition. 3 control siRNA, 3 control estrogen stimulated, 3 siRNA Med12 knockdown, 3 siRNA Med12 knockdown estrogen stimulated, 3 siRNA Smc3 knockdown, 3 siRNA Smc3 knockdown estrogen stimulated.

2013-05-20 | E-GEOD-38252 | biostudies-arrayexpress

Targeting kinome reprogramming in ESR1 fusion-driven metastatic breast cancer

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Whole-genome DNA methylation profiling of ESR1 Q375H and R394H mutations from the human breast cancer MB-231 stable cells.

Project description:Estrogen insensitivity syndrome (EIS) arises from rare mutations in estrogen receptor α (ERα, encoded by ESR1 gene) resulting in the inability of estrogen to exert its biological effects. Due to the rarity, mutations in ESR1 gene and the underlying molecular mechanisms of EIS have not been thoroughly studied. We used human EPIC DNA methylation array to comparison of the transcriptome between the WT ESR1 and Q375H and R394H clinical mutants in MB231 stable cell lines.

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The Chromatin-Looping Factor ZNF143 Engages at Looping Promoters to Favor the Estrogen Response in Breast Cancer (ChIP-seq)

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MED12 mutation activates the tryptophan/kynurenine/AHR pathway to promote growth of uterine leiomyomas

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