Yao Xiang, Jorge Mata-Garrido, Yuanji Fu, Christophe Desterke, Eric Batsché, Ahmed Hamaï, Christine Sedlik, Youssouf Sereme, David Skurnik, Abdelali Jalil, Rachel Onifarasoaniaina, Eric Frapy, Jean-Christophe Beche, Razack Alao, Eliane Piaggio, Laurence Arbibe, Yunhua Chang
As an important immune stimulator and modulator, IFNγ is crucial for gut homeostasis and its dysregulation links to diverse colon pathologies, such as colitis and colorectal cancer (CRC). Here, we demonstrated that the epigenetic regulator, CBX3 (also known as HP1γ) antagonizes IFNγ signaling in the colon epithelium by transcriptionally repressing two critical IFNγ-responsive genes: STAT1 and CD274 (encoding Programmed death-ligand 1, PD-L1). Accordingly, CBX3 deletion resulted in chronic mouse colon inflammation, accompanied by upregulated STAT1 and CD274 expressions...
April 29, 2024: EMBO Molecular Medicine