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An essential role for a mammalian SWI/SNF chromatin-remodeling complex during male meiosis.

ABSTRACT: Germ cell development and gametogenesis require genome-wide transitions in epigenetic modifications and chromatin structure. These changes include covalent modifications to the DNA and histones as well as remodeling activities. Here, we explore the role of the mammalian SWI/SNF chromatin-remodeling complex during spermatogenesis using a conditional allele of the ATPase subunit, brahma-related gene 1 (Brg1, or Smarca4). Not only do BRG1 levels peak during the early stages of meiosis, genetic ablation of Brg1 in murine embryonic gonocytes results in arrest during prophase of meiosis I. Coincident with the timing of meiotic arrest, mutant spermatocytes accumulate unrepaired DNA and fail to complete synapsis. Furthermore, mutant spermatocytes show global alterations to histone modifications and chromatin structure indicative of a more heterochromatic genome. Together, these data demonstrate a requirement for BRG1 activity in spermatogenesis, and suggest a role for the mammalian SWI/SNF complex in programmed recombination and repair events that take place during meiosis.

SUBMITTER: Kim Y

PROVIDER: S-EPMC3283123 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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An essential role for a mammalian SWI/SNF chromatin-remodeling complex during male meiosis.

Kim Yuna Y Fedoriw Andrew M AM Magnuson Terry T

Development (Cambridge, England) 20120208 6

Germ cell development and gametogenesis require genome-wide transitions in epigenetic modifications and chromatin structure. These changes include covalent modifications to the DNA and histones as well as remodeling activities. Here, we explore the role of the mammalian SWI/SNF chromatin-remodeling complex during spermatogenesis using a conditional allele of the ATPase subunit, brahma-related gene 1 (Brg1, or Smarca4). Not only do BRG1 levels peak during the early stages of meiosis, genetic abla ...[more]

PMID: 22318225

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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

An essential role for a mammalian SWI/SNF chromatin-remodeling complex during male meiosis.

Publications

An essential role for a mammalian SWI/SNF chromatin-remodeling complex during male meiosis.

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