# BATF2-mediated control of astrocyte proliferation

## TL;DR

This study shows that BATF2 regulates astrocyte proliferation by controlling cell cycle genes, acting as a suppressor of uncontrolled growth.

## Contribution

BATF2 is newly identified as a key regulator of astrocyte proliferation through its control of cell cycle-related genes.

## Key findings

- Loss of BATF2 increases expression of proliferation markers Ki67 and phospho-histone H3 in astrocytes.
- BATF2 binds to regulatory regions of cell cycle genes like CDK regulatory subunit 1B, CDK2, and cyclin D1.
- Elevated BATF2 levels in glioblastoma samples correlate with decreased cyclin D1 expression.

## Abstract

Astrocyte proliferation in the central nervous system is tightly controlled and is driven by the coordinated expression of regulatory proteins, including cyclins and cyclin-dependent kinases (CDKs), that dictate cell cycle progression. While most of the postnatal proliferation in the central nervous system occurs in well-defined stem cell niches, proliferation of differentiated glial cells can also be observed to maintain local populations during homeostasis and in response to inflammation. However, the transcriptional programs that regulate homeostatic proliferation of terminally differentiated astrocytes are not fully understood. Here, we identify a novel basic leucine zipper ATF-like transcription factor 2 (BATF2) as a prominent regulator of cell cycle genes in astrocytes. Specifically, loss of BATF2 resulted in increased expression of proliferation proteins, including Ki67 and phospho-histone H3. Further, chromatin immunoprecipitation sequencing revealed that BATF2 binds to regulatory regions of several cell cycle–related genes that encode CDK regulatory subunit 1B, CDK2, and cyclin D1 . Concomitantly, we found that deletion of BATF2 increased transcription of these target genes. In addition, we examined the relationship of BATF2 and cyclin D1 in patient-derived glioblastoma samples and found that elevated levels of BATF2 had a corresponding decrease in cyclin D1. Collectively, our study demonstrates that BATF2 participates in the control of astrocytic cell cycle gene expression and further highlights BATF2 as a suppressor of uncontrolled proliferation.