Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes
- 1 July 2002
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 418 (6894), 195-199
- https://doi.org/10.1038/nature00876
Abstract
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.This publication has 23 references indexed in Scilit:
- Ordered Recruitment of Chromatin Modifying and General Transcription Factors to the IFN-β PromoterCell, 2000
- The Swi/Snf familyTrends in Genetics, 2000
- THE REGULATION OF CD4 AND CD8 CORECEPTOR GENE EXPRESSION DURING T CELL DEVELOPMENTAnnual Review of Immunology, 1999
- A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte developmentCell, 1994
- Evidence for a stochastic mechanism in the differentiation of mature subsets of T lymphocytesCell, 1993
- brahma: A regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2SWI2Cell, 1992
- CD8 is needed for development of cytotoxic T but not helper T cellsCell, 1991
- Participation of CD4 coreceptor molecules in T-cell repertoire selectionNature, 1991
- Inhibition of T Cell Receptor Expression and Function in Immature CD4 + cD8 + Cells by CD4Science, 1990
- Five SWI genes are required for expression of the HO gene in yeastJournal of Molecular Biology, 1984