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Promoter-specific functions of CIITA and the MHC class II enhanceosome in transcriptional activation

Published in EMBO Journal. 2002, vol. 21, no. 6, p. 1379-1388
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.
Keywords AcetylationAcetyltransferases/metabolismAntigens, Differentiation, B-Lymphocyte/ geneticsB-Lymphocytes/cytologyCell LineDNA-Binding Proteins/metabolismEnhancer Elements, GeneticGenes, MHC Class IIHLA-D Antigens/ geneticsHLA-DP Antigens/geneticsHLA-DR Antigens/geneticsHistocompatibility Antigens Class II/ geneticsHistone AcetyltransferasesHistones/metabolismHumansNuclear ProteinsPromoter Regions, GeneticSaccharomyces cerevisiae ProteinsTrans-Activators/genetics/ metabolismTranscription Factors/metabolismTranscriptional Activation
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PMID: 11889043
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