# RACK7 Interacts with PRC2 Complex to Regulate Astrocyte Development

## TL;DR

This study shows that RACK7 helps regulate brain development by working with a protein complex to control gene activity in astrocytes.

## Contribution

The study reveals a novel role for RACK7 in regulating astrocyte development through interaction with the PRC2 complex and H3K27me3.

## Key findings

- RACK7 interacts with the PRC2 complex to regulate SUZ12 and H3K27 methylation genomic localization.
- RACK7 deficiency leads to reduced H3K27me3 chromatin localization and astrocyte developmental defects.
- RACK7 and H3K27me3 work together to suppress Wnt signaling and astrocyte differentiation genes.

## 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.

The study investigates the role of RACK7 in brain development using a conditional knockout mouse model. RACK7 deficiency results in developmental defects and abnormal astrocyte development by disrupting H3K27me3 chromatin binding. The underlying mechanism involves RACK7 interacting with the PRC2 complex to regulate the genomic localization of SUZ12 and H3K27me3.