IL-10 transcription is negatively regulated by BAF180, a component of the SWI/SNF chromatin remodeling enzyme

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.In T cells, chromatin structure can be dependent on cell fate, cell activation, or both. This is well illustrated in the case of the Th2 cytokine cluster, containing the Th2 cytokines IL-4, IL-5 and IL-13 [1,2]. The Th2 cytokines are exclusively expressed in Th cells that have differentiated into the Th2 lineage and only upon T cell activation. DNase I hypersensitivity site (DHS) mapping of the cytokine loci from different Th subsets revealed dramatic changes in chromatin accessibility across the locus in Th2 cells compared to other Th lineages and undifferentiated Th precursors (Thps); typically, DHS are nucleosome-free regions created by chromatin remodeling proteins directed by the binding of transcription factors [2,3]. Many of the DHS were subsequently determined both genetically and biochemically to be enhancer and silencer elements important to Th2 cytokine expression and were marked with lineage-specific changes in histone modifications [2,3]. Although changes in nuclease accessibility across cytokine loci in response to differentiation and activation signals have been well documented, less is known about to the specific en