Anthony K N Chan, Li Han, Christopher D Delaney, Xueer Wang, Elizaveta Mukhaleva, Mingli Li, Lu Yang, Sheela Pangeni Pokharel, Nicole Mattson, Michelle Garcia, Bintao Wang, Xiaobao Xu, Leisi Zhang, Priyanka Singh, Zeinab Elsayed, Renee Chen, Benjamin Kuang, Jinhui Wang, Yate-Ching Yuan, Bryan Chen, Lai N Chan, Steven T Rosen, David Horne, Markus Müschen, Jianjun Chen, Nagarajan Vaidehi, Scott A Armstrong, Rui Su, Chun-Wei Chen
Epigenetic dysregulation has been reported in multiple cancers including leukemias. Nonetheless, the roles of the epigenetic reader Tudor domains in leukemia progression and therapy remain unexplored. Here, we conducted a Tudor domain-focused CRISPR screen and identified SGF29, a component of SAGA/ATAC acetyltransferase complexes, as a crucial factor for H3K9 acetylation, ribosomal gene expression, and leukemogenesis. To facilitate drug development, we integrated the CRISPR tiling scan with compound docking and molecular dynamics simulation, presenting a generally applicable strategy called CRISPR-Scan Assisted Drug Discovery (CRISPR-SADD)...
February 23, 2024: Science Advances