title: Two-step binding of transcription factors causes sequential chromatin structural changes at the activated IL-2 promoter.
abstract: Most gene promoters have multiple binding sequences for many transcription factors, but the contribution of each of these factors to chromatin remodeling is still unclear. Although we previously found a dynamic change in the arrangement of nucleosome arrays at the Il2 promoter during T cell activation, its timing preceded that of a decrease in nucleosome occupancy at the promoter. In this article, we show that the initial nucleosome rearrangement was temporally correlated with the binding of NFAT1 and AP-1 (Fos/Jun), whereas the second step occurred in parallel with the recruitment of other transcription factors and RNA polymerase II. Pharmacologic inhibitors for activation of NFAT1 or induction of Fos blocked the initial phase in the sequential changes. This step was not affected, however, by inhibition of c-Jun phosphorylation, which instead blocked the binding of the late transcription factors, the recruitment of CREB-binding protein, and the acetylation of histone H3 at lysine 27. Thus, the sequential recruitment of transcription factors appears to facilitate two separate steps in chromatin remodeling at the Il2 locus.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishihara
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D015153:Blotting, Western; D050882:CREB-Binding Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics* / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D005260:Female; D007376:Interleukin-2 / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D002843:Chromatin; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050882:CREB-Binding Protein