Abstract IA20: Chromatin looping factors and breast cancer

Abstract

Abstract Estrogen signaling in breast cancer cells relies on chromatin interactions connecting distal regulatory elements bound by the estrogen receptor alpha (ER) to target gene promoters. This ensures stimulus and subtype-specific transcriptional responses. Chromatin looping factors, including CTCF, ZNF143 and RAD21, are genetically altered in breast cancer. However, the impact of these alterations on breast cancer development is ill defined. Here we demonstrate that ZNF143 directly regulates the formation of chromatin interactions by marking promoters connecting with distal regulatory elements. ZNF143 occupies the promoter of most early-response estrogen target genes in ER-positive breast cancer cells. Its chromatin occupancy is unaffected by estrogen stimulation suggesting that chromatin interactions are stable as opposed to modulated by stimulus. ZNF143 overexpression within ER-positive breast cancer patients associates with a worse outcome. Its loss abrogates the estrogen response in breast cancer cells. Overall, these results suggest that ZNF143 is a critical effector of the estrogen response and highlights the contribution of the chromatin looping machinery to ER-positive breast cancer development. Citation Format: Aislinn Treloar, Xue Wu, Nadia Penrod, Swneke D. Bailey, Xiaoyang Zhang, Kinjal Desai, Balazs Gyorffy, Mathieu Lupien. Chromatin looping factors and breast cancer. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA20.