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. |