RACK7 recognizes H3.3G34R mutation to suppress expression of MHC class II complex components and their delivery pathway in pediatric glioblastoma
Fangfang Jiao, Ze Li, Chen He, Wenqi Xu, Gensheng Yang, Tingting Liu, Hongjie Shen, Jiajun Cai, Jamie N. Anastas, Ying Mao, Yong‐Chun Yu, Fei Lan, Yujiang Geno Shi, Chris Jones, Yanhui Xu, Suzanne J. Baker, Yang Shi, Rui Guo
Abstract
, which is the master regulator of MHC (major histocompatibility complex) class II molecules and genes involved in vesicular transport of MHC class II molecules to the cell surface, resulting in suppression of MHC class II molecule expression and transport. CRISPR-based knock-in correction of the H3.3G34R mutation in human pediatric glioblastoma (pGBM) cells significantly reduces overall RACK7 chromatin binding and derepresses the same set of genes as does knocking out RACK7 in the H3.3G34R pGBM cells. By demonstrating that H3.3G34R and RACK7 work together, our findings suggest a potential molecular mechanism by which H3.3G34R promotes cancer.