title: Three novel downstream promoter elements regulate MHC class I promoter activity in mammalian cells.
abstract: BACKGROUND
  MHC CLASS I TRANSCRIPTION IS REGULATED BY TWO DISTINCT TYPES OF REGULATORY PATHWAYS: 1) tissue-specific pathways that establish constitutive levels of expression within a given tissue and 2) dynamically modulated pathways that increase or decrease expression within that tissue in response to hormonal or cytokine mediated stimuli. These sets of pathways target distinct upstream regulatory elements, have distinct basal transcription factor requirements, and utilize discrete sets of transcription start sites within an extended core promoter.
  
  
  RESULTS
  We studied regulatory elements within the MHC class I promoter by cellular transfection and in vitro transcription assays in HeLa, HeLa/CIITA, and tsBN462 of various promoter constructs. We have identified three novel MHC class I regulatory elements (GLE, DPE-L1 and DPE-L2), located downstream of the major transcription start sites, that contribute to the regulation of both constitutive and activated MHC class I expression. These elements located at the 3' end of the core promoter preferentially regulate the multiple transcription start sites clustered at the 5' end of the core promoter.
  
  
  CONCLUSIONS
  Three novel downstream elements (GLE, DPE-L1, DPE-L2), located between +1 and +32 bp, regulate both constitutive and activated MHC class I gene expression by selectively increasing usage of transcription start sites clustered at the 5' end of the core promoter upstream of +1 bp. Results indicate that the downstream elements preferentially regulate TAF1-dependent, relative to TAF1-independent, transcription.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Namhoon
authors.initials: N
authors.lastname: Lee
authors.forename: Shankar S
authors.initials: SS
authors.lastname: Iyer
authors.forename: Jie
authors.initials: J
authors.lastname: Mu
authors.forename: Jocelyn D
authors.initials: JD
authors.lastname: Weissman
authors.forename: Anat
authors.initials: A
authors.lastname: Ohali
authors.forename: T Kevin
authors.initials: TK
authors.lastname: Howcroft
authors.forename: Brian A
authors.initials: BA
authors.lastname: Lewis
authors.forename: Dinah S
authors.initials: DS
authors.lastname: Singer
mesh_terms: D000818:Animals; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000378:metabolism; D005805:Genes, MHC Class I; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I; D051548:Histone Acetyltransferases; D006801:Humans; D008957:Models, Genetic; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics; D014018:Tissue Distribution; D035362:Transcription Factor TFIID / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa