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Publication : GATA-3 directly remodels the IL-10 locus independently of IL-4 in CD4+ T cells.

First Author  Shoemaker J Year  2006
Journal  J Immunol Volume  176
Issue  6 Pages  3470-9
PubMed ID  16517715 Mgi Jnum  J:129513
Mgi Id  MGI:3769604 Doi  10.4049/jimmunol.176.6.3470
Citation  Shoemaker J, et al. (2006) GATA-3 directly remodels the IL-10 locus independently of IL-4 in CD4+ T cells. J Immunol 176(6):3470-9
abstractText  IL-10 is a major regulator in inflammatory responses. Although various transcription factors were defined to enhance IL-10, the molecular mechanism for the initiation of Il-10 transcription, remains unknown. mRNA profiling of six distinct primary CD4+ T cell populations showed differential expression of the transcription factor GATA-3 correlated with levels of IL-10 expression. We showed that ectopic expression of GATA-3 in naive primary CD4+ T cells enhanced expression of IL-10 by these cells and uncovered a possible mechanism for this effect. We found that GATA-3 induced changes of the chromatin structure at the Il-10 locus and that these changes occur even in the absence of IL-4. Furthermore we found that in the presence of GATA-3 the histones at the Il-10 locus become acetylated. Despite being recruited in vivo to two locations on the Il-10 locus, GATA-3 did not transactivate the IL-10 promoter. We therefore suggest a key role of GATA-3 in instructing Il-10 gene expression in primary CD4+ T cells, possibly by switching and stabilizing the Il-10 locus into a transcriptionally competent status.
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