IL-10 transcription is negatively regulated by BAF180, a component of the SWI/SNF chromatin remodeling enzyme
1 Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, USA
2 Gene Expression and Genomics Unit, National Institute on Aging Intramural Research Program National Institutes of Health, Baltimore, USA
3 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
4 Current address: National Human Genome Research Institute, NIH, 5635 Fishers Lane, Bethesda, MD 20892, USA
5 Current address: National Institute of Allergy and Infectious Diseases NIH, 6700B Rockledge Drive, Bethesda, MD 20892-7616, USA
BMC Immunology 2012, 13:9 doi:10.1186/1471-2172-13-9Published: 15 February 2012
SWI/SNF chromatin remodeling enzymes play a critical role in the development of T helper lymphocytes, including Th2 cells, and directly program chromatin structure at Th2 cytokine genes. Different versions of SWI/SNF complexes, including BAF and PBAF, have been described based on unique subunit composition. However, the relative role of BAF and PBAF in Th cell function and cytokine expression has not been reported.
Here we examine the role of the PBAF SWI/SNF complex in Th cell development and gene expression using mice deficient for a PBAF-specific component, BAF180. We find that T cell development in the thymus and lymphoid periphery is largely normal when the BAF180 gene is deleted late in thymic development. However, BAF180-deficient Th2 cells express high levels of the immunoregulatory cytokine IL-10. BAF180 binds directly to regulatory elements in the Il-10 locus but is replaced by BAF250 BAF complexes in the absence of BAF180, resulting in increased histone acetylation and CBP recruitment to the IL-10 locus.
These results demonstrate that BAF180 is a repressor of IL-10 transcription in Th2 cells and suggest that the differential recruitment of different SWI/SNF subtypes can have direct consequences on chromatin structure and gene transcription.