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

VR Ramirez-Carrozzi, AA Nazarian, CC Li… - Genes & …, 2006 - genesdev.cshlp.org
VR Ramirez-Carrozzi, AA Nazarian, CC Li, SL Gore, R Sridharan, AN Imbalzano, ST Smale
Genes & development, 2006genesdev.cshlp.org
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 …
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-2β 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-2β complex acting antagonistically to limit the induction of these gene classes. SWI/SNF and Mi-2β 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-2β.
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