H3K27 demethylation by JMJD3 at a poised enhancer of anti-apoptotic gene BCL2 determines ERα ligand dependency.

ABSTRACT: Chromatin represents a repressive barrier to the process of ligand-dependent transcriptional activity of nuclear receptors. Here, we show that H3K27 methylation imposes ligand-dependent regulation of the oestrogen receptor α (ERα)-dependent apoptotic response via Bcl-2 in breast cancer cells. The activation of BCL2 transcription is dependent on the simultaneous inactivation of the H3K27 methyltransferase, EZH2, and the demethylation of H3K27 at a poised enhancer by the ERα-dependent recruitment of JMJD3 in hormone-dependent breast cancer cells. We also provide evidence that this pathway is modified in cells resistant to anti-oestrogen (AE), which constitutively express BCL2. We show that the lack of H3K27 methylation at BCL2 regulatory elements due to the inactivation of EZH2 by the HER2 p

SUBMITTER: Svotelis A 

PROVIDER: S-EPMC3209777 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature