title: Changes in chromatin accessibility across the GM-CSF promoter upon T cell activation are dependent on nuclear factor kappaB proteins.
abstract: Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a key cytokine in myelopoiesis and aberrant expression is associated with chronic inflammatory disease and myeloid leukemias. This aberrant expression is often associated with constitutive nuclear factor (NF)-kappaB activation. To investigate the relationship between NF-kappaB and GM-CSF transcription in a chromatin context, we analyzed the chromatin structure of the GM-CSF gene in T cells and the role of NF-kappaB proteins in chromatin remodeling. We show here that chromatin remodeling occurs across a region of the GM-CSF gene between -174 and +24 upon T cell activation, suggesting that remodeling is limited to a single nucleosome encompassing the proximal promoter. Nuclear NF-kappaB levels appear to play a critical role in this process. In addition, using an immobilized template assay we found that the ATPase component of the SWI/SNF chromatin remodeling complex, brg1, is recruited to the GM-CSF proximal promoter in an NF-kappaB-dependent manner in vitro. These results suggest that chromatin remodeling across the GM-CSF promoter in T cells is a result of recruitment of SWI/SNF type remodeling complexes by NF-kappaB proteins binding to the CD28 response region of the promoter.
authors.affiliation: Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, ACT 2601, Australia.
authors.forename: Adele F
authors.initials: AF
authors.lastname: Holloway
authors.forename: Sudha
authors.initials: S
authors.lastname: Rao
authors.forename: Xinxin
authors.initials: X
authors.lastname: Chen
authors.forename: M Frances
authors.initials: MF
authors.lastname: Shannon
mesh_terms: D018106:CD28 Antigens; D002843:Chromatin / Q000378:metabolism*; D004265:DNA Helicases; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000502:physiology; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D020218:Response Elements; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000502:physiology
chemical_list: D018106:CD28 Antigens; D002843:Chromatin; D016328:NF-kappa B; D009687:Nuclear Proteins; D009707:Nucleosomes; D012333:RNA, Messenger; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C084108:SMARCA4 protein, human; D004265:DNA Helicases