Global role for chromatin remodeling enzymes in mitotic gene expression

Regulation of eukaryotic gene expression requires ATP-dependent chromatin remodeling enzymes, such as SWI/SNF, and histone acetyltransferases, such as Gcn5p. Here we show that SWI/SNF remodeling controls recruitment of Gcn5p HAT activity to many genes in late mitosis and that these chromatin remodeling enzymes play a role in regulating mitotic exit. In contrast, interphase expression of GAL1, HIS3, PHO5, and PHO8 is accompanied by SWI/SNF-independent recruitment of Gcn5p HAT activity. Surprisingly, prearresting cells in late mitosis imposes a requirement for SWI/SNF in recruiting Gcn5p HAT activity to the GAL1 promoter, and GAL1 expression also becomes dependent on both chromatin remodeling enzymes. We propose that SWI/SNF and Gcn5p are globally required for mitotic gene expression due to the condensed state of mitotic chromatin.     

Interferon-gamma-induced chromatin remodeling at the CIITA locus is BRG1 dependent

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)-gamma 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-gamma 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-gamma-responsive GBP-1 gene. Not ably, BRG1 inhibited the CIITA promoter in transient transfection assays, underscoring the importance of an appropriate chromosomal environment. Chromatin immunoprecipitation revealed that BRG1 interacts directly with the endogenous CIITA promoter in an IFN-gamma-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.