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

Wurster AL, Precht P, Becker KG, Wood WH, Zhang Y, Wang Z, Pazin MJ - BMC Immunol. (2012)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, USA.

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

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T cell specific deletion of BAF180 Immunoblot of proteins from wild-type (WT) and BAF180-/- (180) Th2 cells. BAF180 (upper panel) and BRG1 (lower panel) were visualized.
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Figure 1: T cell specific deletion of BAF180 Immunoblot of proteins from wild-type (WT) and BAF180-/- (180) Th2 cells. BAF180 (upper panel) and BRG1 (lower panel) were visualized.

Mentions: As expected, in the presence of the cre recombinase transgene, we observed complete loss of BAF180 protein expression in T cells from BAF180fl/fl mice (Figure 1). By contrast, there was little if any effect on BRG1, another SWI/SNF component. Loss of BAF180 protein expression did not grossly affect cell number from the thymus, spleen or lymph nodes (Figure 2A, B and data not shown) suggesting that overall T cell development and expansion was not strongly affected by the loss of BAF180 at this late stage. This was further supported by FACS analysis showing typical staining profiles for CD4 and CD8 T cell subsets in both the thymus and lymphoid periphery, as well as typical T:B cell ratios in the spleen (Figures 2B, C, D and 3A).


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

Wurster AL, Precht P, Becker KG, Wood WH, Zhang Y, Wang Z, Pazin MJ - BMC Immunol. (2012)

T cell specific deletion of BAF180 Immunoblot of proteins from wild-type (WT) and BAF180-/- (180) Th2 cells. BAF180 (upper panel) and BRG1 (lower panel) were visualized.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3313858&req=5

Figure 1: T cell specific deletion of BAF180 Immunoblot of proteins from wild-type (WT) and BAF180-/- (180) Th2 cells. BAF180 (upper panel) and BRG1 (lower panel) were visualized.
Mentions: As expected, in the presence of the cre recombinase transgene, we observed complete loss of BAF180 protein expression in T cells from BAF180fl/fl mice (Figure 1). By contrast, there was little if any effect on BRG1, another SWI/SNF component. Loss of BAF180 protein expression did not grossly affect cell number from the thymus, spleen or lymph nodes (Figure 2A, B and data not shown) suggesting that overall T cell development and expansion was not strongly affected by the loss of BAF180 at this late stage. This was further supported by FACS analysis showing typical staining profiles for CD4 and CD8 T cell subsets in both the thymus and lymphoid periphery, as well as typical T:B cell ratios in the spleen (Figures 2B, C, D and 3A).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, USA.

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus