The human IL-2 gene promoter can assemble a positioned nucleosome that becomes remodeled upon T cell activation.
Controlled production of the cytokine IL-2 plays a key role in the mammalian immune system. Expression from the gene is tightly regulated with no detectable expression in resting T cells and a strong induction following T cell activation. The IL-2 proximal promoter (+1 to -300) contains many well-defined transcriptional activation elements that respond to T cell stimulation. To determine the role of chromatin structure in the regulation of interleukin-2 gene transcription, nucleosome assembly across the IL-2 promoter region was examined using in vitro chromatin reconstitution assays. The IL-2 promoter assembles a nucleosome that is both translationally and rotationally positioned, spanning some of the major functional control elements. The binding of transcription factors to these elements, with the exception of the architectural protein HMGA1, was occluded by the presence of the nucleosome. Analysis of the chromatin architecture of the IL-2 gene in Jurkat T cells provided evidence for the presence of a similarly positioned nucleosome in vivo. The region encompassed by this nucleosome becomes remodeled following activation of Jurkat T cells. These observations suggest that the presence of a positioned nucleosome across the IL-2 proximal promoter may play an important role in maintaining an inactive gene in resting T cells and that remodeling of this nucleosome is important for gene activation.
Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
Joanne L
JL
Attema
Raymond
R
Reeves
Vincent
V
Murray
Ilya
I
Levichkin
Mark D
MD
Temple
David J
DJ
Tremethick
M Frances
MF
Shannon
D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018983:DNA Footprinting; D004273:DNA, Neoplasm / Q000032:analysis; D025741:HMGA1a Protein / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D014176:Protein Biosynthesis / Q000276:immunology; D020218:Response Elements / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
D018106:CD28 Antigens; D002843:Chromatin; D004273:DNA, Neoplasm; D007376:Interleukin-2; D009707:Nucleosomes; D014157:Transcription Factors; D025741:HMGA1a Protein