title: Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site.
abstract: Nucleosome depletion at transcription start sites (TSS) has been documented genome-wide in multiple eukaryotic organisms. However, the mechanisms that mediate this nucleosome depletion and its functional impact on transcription remain largely unknown. We have studied these issues at human MHC class II (MHCII) genes. Activation-induced nucleosome free regions (NFR) encompassing the TSS were observed at all MHCII genes. Nucleosome depletion was exceptionally strong, attaining over 250-fold, at the promoter of the prototypical HLA-DRA gene. The NFR was induced primarily by the transcription factor complex that assembles on the conserved promoter-proximal enhancer situated upstream of the TSS. Functional analyses performed in the context of native chromatin demonstrated that displacing the NFR without altering the sequence of the core promoter induced a shift in the position of the TSS. The NFR thus appears to play a critical role in transcription initiation because it directs correct TSS positioning in vivo. Our results provide support for a novel mechanism in transcription initiation whereby the position of the TSS is controlled by nucleosome eviction rather than by promoter sequence.
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1 rue Michel-Servet, CH-1211, Geneva, Switzerland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Leimgruber
authors.forename: Queralt
authors.initials: Q
authors.lastname: Seguín-Estévez
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dunand-Sauthier
authors.forename: Natalia
authors.initials: N
authors.lastname: Rybtsova
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Schmid
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ambrosini
authors.forename: Philipp
authors.initials: P
authors.lastname: Bucher
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics; D059805:HLA-DR alpha-Chains; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009707:Nucleosomes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site
chemical_list: D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D009707:Nucleosomes; D007371:Interferon-gamma