GATA-3 directly remodels the IL-10 locus independently of IL-4 in CD4+ T cells.
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.
Shoemaker
John
J
Division of Immunoregulation, National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom.
Saraiva
Margarida
M
O'Garra
Anne
A
D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D015533:Transcriptional Activation / Q000235:genetics
D002843:Chromatin; D050990:GATA3 Transcription Factor; D006657:Histones; D016753:Interleukin-10; D015847:Interleukin-4