MYC is a well characterized oncogenic transcription factor in prostate cancer, and CTCF is the main architectural protein of three-dimensional genome organization. However, the functional link between the two master regulators has not been reported. In this study, we find that MYC rewires prostate cancer chromatin architecture by interacting with CTCF protein. Through combining the H3K27ac, AR and CTCF HiChIP profiles with CRISPR deletion of a CTCF site upstream of MYC gene, we show that MYC activation leads to profound changes of CTCF-mediated chromatin looping. Mechanistically, MYC colocalizes with CTCF at a subset of genomic sites, and enhances CTCF occupancy at these loci. Consequently, the CTCF-mediated chromatin looping is potentiated by MYC activation, resulting in the disruption of enhancer-promoter looping at neuroendocrine lineage plasticity genes. Collectively, our findings define the function of MYC as a CTCF co-factor in three-dimensional genome organization.
Nature communications. 2023 Mar 30*** epublish ***
Zhao Wei, Song Wang, Yaning Xu, Wenzheng Wang, Fraser Soares, Musaddeque Ahmed, Ping Su, Tingting Wang, Elias Orouji, Xin Xu, Yong Zeng, Sujun Chen, Xiaoyu Liu, Tianwei Jia, Zhaojian Liu, Lutao Du, Yunshan Wang, Shaoyong Chen, Chuanxin Wang, Housheng Hansen He, Haiyang Guo
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, China., Department of Clinical Laboratory, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, Shandong, China., Princess Margaret Cancer Center/University Health Network, Toronto, Ontario, M5G 1L7, Canada., National Administration of Health Data, Jinan, 250000, China., Institute of Medical Sciences, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, Shandong, China., Epigenetics Initiative, Princess Margaret Genomics Centre, Toronto, ON, Canada., Key Laboratory of Experimental Teratology, Ministry of Education, Department of Cell Biology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China., Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Princess Margaret Cancer Center/University Health Network, Toronto, Ontario, M5G 1L7, Canada. ., Department of Clinical Laboratory, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, Shandong, China. .