OUP accepted manuscript

2019 Nucleic Acids Research  
Estrogen receptor ␣ (ER␣) is an enhancer activating transcription factor, a key driver of breast cancer and a main target for cancer therapy. ER␣mediated gene regulation requires proper chromatinconformation to facilitate interactions between ER␣bound enhancers and their target promoters. A major determinant of chromatin structure is the CCCTCbinding factor (CTCF), that dimerizes and together with cohesin stabilizes chromatin loops and forms the boundaries of topologically associated domains.
more » ... wever, whether CTCF-binding elements (CBEs) are essential for ER␣-driven cell proliferation is unknown. To address this question in a global manner, we implemented a CRISPR-based functional genetic screen targeting CBEs located in the vicinity of ER␣bound enhancers. We identified four functional CBEs and demonstrated the role of one of them in inducing chromatin conformation changes in favor of activation of PREX1, a key ER␣ target gene in breast cancer. Indeed, high PREX1 expression is a bona-fide marker of ER␣-dependency in cell lines, and is associated with good outcome after anti-hormonal treatment. Altogether, our data show that distinct CTCFmediated chromatin structures are required for ER␣driven breast cancer cell proliferation.
doi:10.1093/nar/gkz675 fatcat:sdaa677vfnemzekvy7hkdaq3c4