title: The class II transactivator requires brahma-related gene 1 to activate transcription of major histocompatibility complex class II genes.
abstract: The class II transactivator (CIITA) is the key regulator of major histocompatibility complex (MHC) class II gene transcription. We demonstrate here that CIITA requires the ATPase subunit of an hSWI/SNF complex, brahma-related gene 1 (BRG-1), to activate transcription. When introduced into a cell line lacking BRG-1, CIITA was unable to activate cellular MHC class II genes. Reexpression of the wild-type but not an ATP-binding-deficient BRG-1 protein in this cell line restored the ability of CIITA to transactivate transcription of MHC class II genes. Interestingly, when the activity of CIITA was assayed in the BRG-1-deficient cell line by using a plasmid-based reporter assay, BRG-1 was not required for transcriptional activation, suggesting that the chromatin structure on the plasmid is such that BRG-1 is not necessary. Coimmunoprecipitation experiments were performed to determine if BRG-1 and CIITA proteins associate with each other in cells. We found that the two proteins coimmunoprecipitate and that amino acids 1 to 140 of CIITA are sufficient for binding. Taken together, these data suggest that BRG-1 and, very likely, an hSWI/SNF complex are required for transcription of MHC class II genes. The complex is likely recruited to MHC class II promoters, at least in part, by interaction with CIITA.
authors.affiliation: Department of Biological, Geological and Environmental Sciences, Cleveland State University, 2399 Euclid Avenue, Cleveland, OH 44115, USA.
authors.forename: Rajini
authors.initials: R
authors.lastname: Mudhasani
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fontes
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D004265:DNA Helicases; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics; D059805:HLA-DR alpha-Chains; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D021122:Protein Subunits; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D021122:Protein Subunits; D015534:Trans-Activators; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C084108:SMARCA4 protein, human; D004265:DNA Helicases