Chromatin modifiers - Coordinators of estrogen action

Abstract

A group of hormones, called estrogens, are pivotal drivers of various physiological processes. Expectedly, estrogen-driven actions are also relevant modulators of pathophysiological changes, including cancer. Different transcriptional and tissue-specific responses are elicited mainly by two estrogen receptor (ER) isoforms, ERα and ERβ. Although perturbations of ER subtype-specific expression are correlated with clinical outcomes of cancer, the result strongly depends on co-regulators. Co-regulator acts as a 'bridge' that helps form large protein complexes to modulate transcriptional activity on target gene chromatin. ERs, as transcription factors, may be positively or negatively influenced by the utilisation of different tissue-specific co-regulators. These co-regulators are enzymes that create the epigenetic landscape of histone and DNA modifications, along with proteins that read these modifications and ATP-dependent chromatin remodelers. This review provides an overview and update on ER-driven responses, focusing on the complex interaction between ERs and chromatin modifiers, and discusses how chromatin accessibility and epigenetic modifications contribute to ER recruitment and transactivation.

Keywords: Chromatin modifiers; Epigenetics; Estrogen; Estrogen receptors.