Jie Luo, Zhixiang Chen, Yuanyuan Qiao, Jean Ching-Yi Tien, Eleanor Young, Rahul Mannan, Somnath Mahapatra, Tongchen He, Sanjana Eyunni, Yuping Zhang, Yang Zheng, Fengyun Su, Xuhong Cao, Rui Wang, Yunhui Cheng, Rithvik Seri, James George, Miriam Shahine, Stephanie J Miner, Ulka Vaishampayan, Mi Wang, Shaomeng Wang, Abhijit Parolia, Arul M Chinnaiyan
Prostate cancer is an exemplar of an enhancer-binding transcription factor-driven disease. The androgen receptor (AR) enhanceosome complex comprised of chromatin and epigenetic coregulators assembles at enhancer elements to drive disease progression. The paralog lysine acetyltransferases p300 and CBP deposit histone marks that are associated with enhancer activation. Here, we demonstrate that p300/CBP are determinant cofactors of the active AR enhanceosome in prostate cancer. Histone H2B N-terminus multisite lysine acetylation (H2BNTac), which was exclusively reliant on p300/CBP catalytic function, marked active enhancers and was notably elevated in prostate cancer lesions relative to the adjacent benign epithelia...
March 30, 2024: bioRxiv