Department of Histology and Embryology, Poznan University of Medical Sciences, Poland.
Department of Histology and Embryology, Poznan University of Medical Sciences, Poland; Department of Head and Neck Surgery, Poznan University of Medical Sciences, The Greater Poland Cancer Centre, Poland.
Biomed Pharmacother. 2022 Sep;153:113548. doi: 10.1016/j.biopha.2022.113548. Epub 2022 Aug 17.
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.
一组被称为雌激素的激素是各种生理过程的关键驱动因素。可以预期,雌激素驱动的作用也是病理生理变化的相关调节剂,包括癌症。不同的转录和组织特异性反应主要由两种雌激素受体 (ER) 同工型 ERα 和 ERβ 引起。尽管 ER 亚型特异性表达的扰动与癌症的临床结果相关,但结果强烈取决于共调节剂。共调节剂作为“桥梁”,有助于形成大型蛋白质复合物,调节靶基因染色质上的转录活性。作为转录因子的 ER 可能受到不同组织特异性共调节剂利用的正或负影响。这些共调节剂是酶,它们在组蛋白和 DNA 修饰的表观遗传景观上发挥作用,以及读取这些修饰和 ATP 依赖性染色质重塑剂的蛋白质。这篇综述提供了对 ER 驱动反应的概述和更新,重点讨论了 ER 与染色质修饰剂之间的复杂相互作用,并讨论了染色质可及性和表观遗传修饰如何有助于 ER 募集和转录激活。