GADD45G operates as a pathological sensor orchestrating reactive gliosis and neurodegeneration [ChIP-seq]

GADD45G functions as stress sensors and plays critical roles in the regulation of cell cycles, DNA repair, apoptosis and inflammation. They are localized in both the nucleus and the cytoplasm and carry out their specific functions through protein-protein interactions, the demethylase activity, and regulation of intracellular signaling pathways. The role of GADD45G in astrocytes is completely unknown. On the other hand, GADD45G is consistently upregulated under different pathological stimuli in astrocytes. Therefore, we decided to assess the function of GADD45G in astrocytes. In this study, we showed the GADD45G signaling in astrocytes drives a distinct pathogenic reactivity state both in vitro and in vivo. We also explore the communication between GADD45G-driven astrocytes and other cells in the CNS, including microglia and neurons, and discuss how this crosstalk regulates CNS inflammation and pathological outcomes. ChIP-seq of in vitro culture astrocytes expressing FLAG or FLAG-GADD45G. Primary WT astrocytes were cultured with serum-free medium, transduced with lentivirus (LV-hGFAP-FLAG or LV-hGFAP-FLAG-GADD45G).