The proteasome inhibitor bortezomib induces an inhibitory chromatin environment at a distal enhancer of the estrogen receptor-α gene.

ABSTRACT: Expression of the estrogen receptor-α (ERα) gene, ESR1, is a clinical biomarker used to predict therapeutic outcome of breast cancer. Hence, there is significant interest in understanding the mechanisms regulating ESR1 gene expression. Proteasome activity is increased in cancer and we previously showed that proteasome inhibition leads to loss of ESR1 gene expression in breast cancer cells. Expression of ESR1 mRNA in breast cancer cells is controlled predominantly through a proximal promoter within ∼400 base pair (bp) of the transcription start site (TSS). Here, we show that loss of ESR1 gene expression induced by the proteasome inhibitor bortezomib is associated with inactivation of a distal enhancer located 150 kilobases (kb) from the TSS. Chromatin immunoprecipitation assays reveal sever

SUBMITTER: Powers GL 

PROVIDER: S-EPMC3855213 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature