Chromatin remodeler Chd7 regulates reactive astrogliosis after ischemic stroke

Reactive astrogliosis, characterized by profound changes in astrocytic phenotype in response to central nervous system (CNS) insults such as ischemic stroke, plays a crucial role in the pathophysiology of CNS injury. However, the mechanisms underlying its transcriptional regulation remain largely unknown. We demonstrate that Chd7 regulates reactive astrogliosis after ischemic stroke. Chd7 expression is induced in a subset of reactive astrocytes in the peri-infarct cortex, concomitant with increased Sox2 and Atf4 expression. Astrocyte-specific deletion of Chd7 in injured mice reduces reactive astrocyte proliferation, lesion volume, astrocytic scar formation, and neuroinflammation and improves motor recovery following stroke. Mechanistically, Chd7 forms complexes with either Sox2 or Atf4 and binds the Trib3 promoter, directly regulating Trib3 transcription to promote astrocyte proliferation, whereas the Chd7-Sox2 complex regulates interleukin-1β induction via direct transcriptional regulation of C3ar1 and Malt1. Thus, Chd7 functions as a key regulator of reactive astrogliosis in concert with Sox2 or Atf4.