Promoter-specific functions of CIITA and the MHC class II enhanceosome in transcriptional activation.
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.
Masternak
Krzysztof
K
Department of Genetics and Microbiology, University of Geneva Medical School, 1 rue Michel-Servet, CH-1211 Genève 4, Switzerland.
Reith
Walter
W
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
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