Selective and antagonistic functions of SWI/SNF and Mi-2β nucleosome remodeling complexes during an inflammatory response

Abstract

Studies of mammalian genes activated in response to an acute stimulus have suggested diverse mechanisms through which chromatin structure and nucleosome remodeling events contribute to inducible gene transcription. However, because of this diversity, the logical organization of the genome with respect to nucleosome remodeling and gene induction has remained obscure. Numerous proinflammatory genes are rapidly induced in macrophages in response to microbial infection. Here, we show that in lipopolysaccharide-stimulated macrophages, the catalytic BRG1/BRM subunits of the SWI/SNF class of ATP-dependent nucleosome remodeling complexes are consistently required for the activation of secondary response genes and primary response genes induced with delayed kinetics, but not for rapidly induced primary response genes. Surprisingly, a Mi-2␤ complex was selectively recruited along with the SWI/SNF complexes to the control regions of secondary response and delayed primary response genes, with the Mi-2␤ complex acting antagonistically to limit the induction of these gene classes. SWI/SNF and Mi-2␤ complexes influenced cell size in a similarly antagonistic manner. These results provide insight into the differential contributions of nucleosome remodeling complexes to the rapid induction of defined classes of mammalian genes and reveal a robust anti-inflammatory function of Mi-2␤.[Keywords: Inflammation; cytokines; chromatin; SWI/SNF; NuRD] Supplemental material is available at http://www.genesdev.org.

Toward an Understanding of the Gene-Specific and Global Logic of Inducible Gene Transcription

“…1) (Weinmann et al 1999;Ramirez-Carrozzi et al 2006). Similar results were later obtained with the Il12b enhancer ( Fig.…”

Regulation and function of TPL-2, an IκB kinase-regulated MAP kinase kinase kinase

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“…4B), indicating that its expression requires de novo protein synthesis. These data place tenascin-C in the group of secondary inflammatory response genes (that includes IL-6 and IL-12), which require new protein synthesis for both transcription and nucleosome remodeling (33).…”