Dataset Information

Molecular basis of CD4 repression by the Swi/Snf-like BAF chromatin remodeling complex.

ABSTRACT: The Brg1/Brm-associated factor (BAF) chromatin remodeling complex directly binds the CD4 silencer and is essential for CD4 repression during T-cell development, because deletion of the ATPase subunit Brg1 or a dominant negative mutant of BAF57 each impairs CD4 repression in early thymocytes. Paradoxically, BAF57 is dispensable for remodeling nucleosomes in vitro or for binding of the BAF complex to the CD4 silencer in vivo. Thus, it is unclear whether BAF57-dependent CD4 repression involves chromatin remodeling and, if so, how the remodeling translates into CD4 repression. Here we show that nucleosomes at the CD4 silencer occupy multiple translational frames. BAF57 dominant negative mutant does not alter these frames, but reduces the accessibility of the entire silencer without affecting the flanking regions, concomitant with localized accumulation of linker histone H1 and eviction of Runx1, a key repressor of CD4 transcription that directly binds the CD4 silencer. Our data indicate that precise nucleosome positioning is not critical for the CD4 silencer function and that BAF57 participates in remodeling H1-containing chromatin at the CD4 silencer, which enables Runx1 to access the silencer and repress CD4. In addition to BAF57, multiple other subunits in the BAF complex are also dispensable for chromatin remodelling in vitro. Our data suggest that these subunits could also help remodel chromatin at a step after the recruitment of the BAF complex to target genes.

SUBMITTER: Wan M

PROVIDER: S-EPMC2774848 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Molecular basis of CD4 repression by the Swi/Snf-like BAF chromatin remodeling complex.

Wan Mimi M Zhang Jianmin J Lai Dazhi D Jani Anant A Prestone-Hurlburt Paula P Zhao Lulu L Ramachandran Aruna A Schnitzler Gavin R GR Chi Tian T

European journal of immunology 20090201 2

The Brg1/Brm-associated factor (BAF) chromatin remodeling complex directly binds the CD4 silencer and is essential for CD4 repression during T-cell development, because deletion of the ATPase subunit Brg1 or a dominant negative mutant of BAF57 each impairs CD4 repression in early thymocytes. Paradoxically, BAF57 is dispensable for remodeling nucleosomes in vitro or for binding of the BAF complex to the CD4 silencer in vivo. Thus, it is unclear whether BAF57-dependent CD4 repression involves chro ...[more]

PMID: 19180471

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Project description:UnlabelledWongabel virus (WONV) is an arthropod-borne rhabdovirus that infects birds. It is one of the growing array of rhabdoviruses with complex genomes that encode multiple accessory proteins of unknown function. In addition to the five canonical rhabdovirus structural protein genes (N, P, M, G, and L), the 13.2-kb negative-sense single-stranded RNA (ssRNA) WONV genome contains five uncharacterized accessory genes, one overlapping the N gene (Nx or U4), three located between the P and M genes (U1 to U3), and a fifth one overlapping the G gene (Gx or U5). Here we show that WONV U3 is expressed during infection in insect and mammalian cells and is required for efficient viral replication. A yeast two-hybrid screen against a mosquito cell cDNA library identified that WONV U3 interacts with the 83-amino-acid (aa) C-terminal domain of SNF5, a component of the SWI/SNF chromatin remodeling complex. The interaction was confirmed by affinity chromatography, and nuclear colocalization was established by confocal microscopy. Gene expression studies showed that SNF5 transcripts are upregulated during infection of mosquito cells with WONV, as well as West Nile virus (Flaviviridae) and bovine ephemeral fever virus (Rhabdoviridae), and that SNF5 knockdown results in increased WONV replication. WONV U3 also inhibits SNF5-regulated expression of the cytokine gene CSF1. The data suggest that WONV U3 targets the SWI/SNF complex to block the host response to infection.ImportanceThe rhabdoviruses comprise a large family of RNA viruses infecting plants, vertebrates, and invertebrates. In addition to the major structural proteins (N, P, M, G, and L), many rhabdoviruses encode a diverse array of accessory proteins of largely unknown function. Understanding the role of these proteins may reveal much about host-pathogen interactions in infected cells. Here we examine accessory protein U3 of Wongabel virus, an arthropod-borne rhabdovirus that infects birds. We show that U3 enters the nucleus and interacts with SNF5, a component of the chromatin remodeling complex that is upregulated in response to infection and restricts viral replication. We also show that U3 inhibits SNF5-regulated expression of the cytokine colony-stimulating factor 1 (CSF1), suggesting that it targets the chromatin remodeling complex to block the host response to infection. This study appears to provide the first evidence of a virus targeting SNF5 to inhibit host gene expression.

Dataset Information

Molecular basis of CD4 repression by the Swi/Snf-like BAF chromatin remodeling complex.

Publications

Molecular basis of CD4 repression by the Swi/Snf-like BAF chromatin remodeling complex.

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