Abhijit Parolia, Sanjana Eyunni, Brijesh Kumar Verma, Eleanor Young, Lianchao Liu, James George, Shweta Aras, Chandan Kanta Das, Rahul Mannan, Reyaz Ur Rasool, Jie Luo, Sandra E Carson, Erick Mitchell-Velasquez, Yihan Liu, Lanbo Xiao, Prathibha R Gajjala, Mustapha Jaber, Tongchen He, Yuanyuan Qiao, Matthew Pang, Yuping Zhang, Mohammed Alhusayan, Xuhong Cao, Omid Tavana, Caiyun Hou, Zhen Wang, Ke Ding, Arul M Chinnaiyan, Irfan A Asangani
The androgen receptor (AR) is a ligand-responsive transcription factor that binds at enhancers to drive terminal differentiation of the prostatic luminal epithelia. By contrast, in tumors originating from these cells, AR chromatin occupancy is extensively reprogrammed to drive hyper-proliferative, metastatic, or therapy-resistant phenotypes, the molecular mechanisms of which remain poorly understood. Here, we show that the tumor-specific enhancer circuitry of AR is critically reliant on the activity of Nuclear Receptor Binding SET Domain Protein 2 (NSD2), a histone 3 lysine 36 di-methyltransferase...
March 1, 2024: bioRxiv