RACK7 Interacts with PRC2 Complex to Regulate Astrocyte Development

Abstract

Dysregulation of epigenetic mechanisms plays a crucial role in brain development and disease. Emerging largely evidence suggests that Receptor for Activated C-kinase 7 (RACK7), an epigenetic reader protein, may play a role in brain development and neural developmental disease, but in vivo explorations are still lacking. Here, a Rack7 conditional knock-out mouse model is established and shows that Rack7-deficient mice exhibit overt developmental defects associated with aberrant astrocyte development. Mechanistically, it is found that RACK7 interacts with the histone H3 lysine 27 (H3K27) methyltransferase, i.e., the Polycomb Repressive Complex 2 (PRC2) complex, to establish the genomic locations of Suppressor of Zeste 12 homolog (SUZ12) and H3K27 methylation. Deletion of Rack7 in astrocytes leads to a remarkable decrease of H3K27me3 chromatin localization genome-wide. Furthermore, RACK7 works together with H3K27me3 to prevent overactivation of the Wnt signaling pathway and other astrocyte differentiation genes are found. Collectively, this study provides new insights into the cellular and molecular mechanisms underlying brain development regulated by RACK7.