LAUSR

Estrogen Receptor α (ERα) is expressed in ER+ breast cancers, one of the leading causes of death among women. Despite effectiveness of endocrine therapy, a significant number of patients experience resistance to these treatments. One of the major hurdles is lack of comprehensive information about ERα transcriptional complex activity. While biochemical assays have improved our knowledge significantly, it is critical to imply techniques that allow direct visualization of ERα activity and gain spatiotemporal information. We used super resolution microscopy to examine the mechanism of ERα transcriptional activity. We showed that ERα interactions with its co-activators (P300, SRC-3), is influenced upon administration of Tamoxifen and Fulvestrant, an effect that is lost in cells carrying multination in ERα ligand binding site. Additionally mutant cells are no longer able to recruit ERα co-inhibitor (NCORI). Using STORM microscopy, we showed estrogen treatment caused an “open” chromatin (H3K27ac) structure which may represent active areas of gene expression, while Tamoxifen and Fulvestrant treatments caused chromatin to form “closed” structures which likely represent close and inactive phase of chromatin. Citation Format: Tara Akhshi, Myles Brown. Defining the mechanism of ER receptor transcription complex activity and its effect on epigenetic modulations using super resolution microscopy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3717.