Interferon-γ resets muscle cell fate by stimulating the sequential recruitment of JARID2 and PRC2 to promoters to repress myogenesis.

ABSTRACT: The inflammatory cytokine interferon-γ (IFN-γ) orchestrates a diverse array of fundamental physiological processes. IFN-γ and the class II transactivator (CIITA) play essential roles in inhibiting muscle development during the inflammatory response. We describe the mechanism through which IFN-γ and CIITA inhibit myogenesis by repressing gene expression in muscle cells subjected to inflammation. In mice, the presence of increased amounts of circulating IFN-γ resulted in the increased abundance of Polycomb repressive complex 2 (PRC2) in muscle fibers, a tissue in which PRC2 is not normally present in the adult. We showed that CIITA first interacted with the Jumonji family protein JARID2, a noncatalytic subunit of PRC2, which caused an RNA polymerase II (RNAPII), phosphorylated at serine-5, t

SUBMITTER: Londhe P 

PROVIDER: S-EPMC4000160 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature