Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta-cell apoptosis.

Chronic free fatty acid (FFA) exposure induces pancreatic beta-cell death, which may contribute to the development of type 2 diabetes. The mechanisms involved in FFA-induced cell death are not completely understood. Here we have investigated the effect of FFA on endoplasmic reticulum (ER) stress pathways in INS-1 pancreatic beta-cells.

Apical role for BRG1 in cytokine-induced promoter assembly.

IFN-gamma induction of the CIITA (class II transactivator) promoter (pIV) requires Brahma-related gene 1 (BRG1), a chromatin-remodeling enzyme. However, the events that lead to pIV activation are only partially understood, and the point at which BRG1 acts is unknown. The first IFN-gamma-induced event triggers nuclear translocation of STAT1 (signal transducer and activator of transcription 1), which binds IFN-gamma-responsive promoters.

Murine cytomegalovirus paralyzes macrophages by blocking IFN gamma-induced promoter assembly.

Macrophages (M phi) are activated by IFN gamma and are important cellular targets for infection by human and murine cytomegalovirus (MCMV), making it advantageous for CMVs to block IFN gamma-induced M phi differentiation. We found that MCMV infection inhibited IFN gamma regulation of many genes in M phi. MCMV infection blocked IFN gamma responses at the level of transcription without blocking Janus kinase/signal transducer and activator of transcription pathway activation and targeted IFN response factor 1- and class II transactivator-dependent and independent promoters.

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.