OR16-3 Analysis of Testis-Enriched Genes in Estrogen-Dependent Genome Regulation in Breast Cancer

Abstract Emerging studies show that testis-enriched genes play critical roles in several biological processes. The expression of these is tightly regulated and limited to immune-privileged organs; however, many them escape regulation are aberrantly expressed diseases such as cancer. Intriguingly, our genomic analysis revealed transcribed from previously considered gene deserts. We also found a significant number robustly by estrogen other peptide hormones Tumor Necrosis Factor-alpha (TNF alpha). However, their direct role estrogen-dependent transcriptional outcomes remains unstudied. In this regard, integrated approach, including RNA with 4-thiouridine (4sU) coupled RNA-sequencing CRISPR-based genetic screening, has identified key estrogen-regulated may modulate estrogen-signaling. Through series molecular phenotypic assays, we selected potential but understudied transcript, which predominantly localized the nucleus. Furthermore, current study, have interrogated functional mechanisms transcript controls receptor-positive (ER+) breast cell tumor growth. Additionally, manipulated levels estrogen-receptor-positive cancer cells employing gain- loss-of-function performed 4sU-RNA-seq. Interestingly, modulates estrogen-driven transcripts ER-alpha (ERa) binding sites. Mechanistically, nucleus interacts chromatin-associated proteins. addition, analyses comprising 'Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq)' 'chromatin immunoprecipitation (ChIP) massively parallel DNA ChIP-seq' (H3K27ac, H3K27me3) controlling epigenetic landscape at target promoters enhancers ER+ Collectively, data support enhancer transcription chromatin organization. This study sheds light on functions presents an opportunity identify new diagnostic develop treatment strategies S.S.G. supported grant Cancer Prevention Research Institute Texas (CPRIT; RR170020). Lizanell Colbert Coldwell foundation. Presentation: Sunday, June 12, 2022 11:30 a.m. - 11:45