Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes
doi: 10.1038/nature00876
pmid: 12110891
Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes
Thymic development produces two sub-lineages of T cells expressing either CD4 or CD8 co-receptors that assist antibody production and mediate cell killing, respectively. The mechanisms for mutually exclusive co-receptor expression remain poorly defined. We find that mutations in the high mobility group (HMG) domain of BAF57--a DNA-binding subunit of the mammalian SWI/SNF-like chromatin-remodelling BAF complexes--or in the BAF complex ATPase subunit Brg, impair both CD4 silencing and CD8 activation. Brg is haploinsufficient for CD8 activation, but not for CD4 silencing, whereas BAF57 mutations preferentially impair CD4 silencing, pointing to target- and subunit-specific mechanisms of chromatin remodelling. BAF complexes directly bind the CD4 silencer, but the BAF57 HMG domain is dispensable for tethering BAF complexes to the CD4 silencer or other chromatin loci in vivo, or for remodelling reconstituted templates in vitro, suggesting that chromatin remodelling in vivo requires HMG-dependent DNA bending. These results indicate that BAF complexes contribute to lineage bifurcation by reciprocally regulating lineage-specific genes, reminiscent of the role of the yeast SWI/SNF complex in mediating mating-type switching.
- Stanford University United States
- New York University United States
- Howard Hughes Medical Institute United States
- National Institute of Health Pakistan
Macromolecular Substances, CD8 Antigens, DNA Helicases, Nuclear Proteins, Mice, Transgenic, Thymus Gland, Flow Cytometry, Chromatin, Protein Structure, Tertiary, DNA-Binding Proteins, Mice, Protein Subunits, Cross-Linking Reagents, Gene Expression Regulation, CD4 Antigens, Mutation, Animals, Gene Silencing, Protein Binding, Transcription Factors
Macromolecular Substances, CD8 Antigens, DNA Helicases, Nuclear Proteins, Mice, Transgenic, Thymus Gland, Flow Cytometry, Chromatin, Protein Structure, Tertiary, DNA-Binding Proteins, Mice, Protein Subunits, Cross-Linking Reagents, Gene Expression Regulation, CD4 Antigens, Mutation, Animals, Gene Silencing, Protein Binding, Transcription Factors
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