title: Promoter-specific functions of CIITA and the MHC class II enhanceosome in transcriptional activation.
abstract: Transcription of the major histocompatibility complex class II family of genes is regulated by conserved promoter elements and two gene-specific trans-activators, RFX and CIITA. RFX binds DNA and nucleates the assembly of an enhanceosome, which recruits CIITA through protein--protein interactions. Transcriptional activation is a complex, multi-step process involving chromatin modification and recruitment of the transcription apparatus. To examine the roles of the enhanceosome and CIITA in these processes, we analysed the level of promoter-associated hyperacetylated histones H3 and H4, TBP, TFIIB and RNA poly merase II in cells lacking RFX or CIITA. We compared four genes co-regulated by RFX and CIITA (HLA-DRA, HLA-DPB, HLA-DMB and Ii) and found that the enhanceosome and CIITA make variable, promoter-dependent contributions to histone acetylation and transcription apparatus recruitment. CIITA is generally implicated at multiple levels of the activation process, while the enhanceosome contributes in a CIITA-independent manner only at certain promoters. Our results support the general notion that the impact of a particular activator on transcription in vivo may vary depending on the promoter and the chromatin context.
authors.affiliation: Department of Genetics and Microbiology, University of Geneva Medical School, 1 rue Michel-Servet, CH-1211 Genève 4, Switzerland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Masternak
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics*; D001402:B-Lymphocytes / Q000166:cytology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics*; D006682:HLA-DP Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059805:HLA-DR alpha-Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D004268:DNA-Binding Proteins; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D000949:Histocompatibility Antigens Class II; D006657:Histones; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C045084:invariant chain; D000123:Acetyltransferases; D051548:Histone Acetyltransferases