Premium
Interferon‐γ‐induced chromatin remodeling at the CIITA locus is BRG1 dependent
Author(s) -
Pattenden Samantha G.,
Klose Robert,
Karaskov Elizabeth,
Bremner Rod
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.8.1978
Subject(s) - library science , computer science
SWI/SNF regulates growth control, differentiation and tumor suppression, yet few direct targets of this chromatin‐remodeling complex have been identified in mammalian cells. We report that SWI/SNF is required for interferon (IFN)‐γ induction of CIITA, the master regulator of major histocompatibility complex class II expression. Despite the presence of functional STAT1, IRF‐1 and USF‐1, activators implicated in CIITA expression, IFN‐γ did not induce CIITA in cells lacking BRG1 and hBRM, the ATPase subunits of SWI/SNF. Reconstitution with BRG1, but not an ATPase‐deficient version of this protein (K798R), rescued CIITA induction, and enhanced the rate of induction of the IFN‐γ‐responsive GBP‐1 gene. Not ably, BRG1 inhibited the CIITA promoter in transient transfection assays, underscoring the importance of an appropriate chromosomal environment. Chroma tin immunoprecipitation revealed that BRG1 interacts directly with the endogenous CIITA promoter in an IFN‐γ‐inducible fashion, while in vivo DNase I footprinting and restriction enzyme accessibility assays showed that chromatin remodeling at this locus requires functional BRG1. These data provide the first link between a cytokine pathway and SWI/SNF, and suggest a novel role for this chromatin‐remodeling complex in immune surveillance.