Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITA

Krawczyk, Michal; Peyraud, Nicolas; Rybtsova, Natalia; Masternak, Krzysztof; Bucher, Philipp; Barras, Emmanuele; Reith, Walter

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Title		Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITA
Authors		Krawczyk, Michal Peyraud, Nicolas Rybtsova, Natalia Masternak, Krzysztof Bucher, Philipp Barras, Emmanuele Reith, Walter
Published in		Journal of Immunology. 2004, vol. 173, no. 10, p. 6200-6210
Abstract		MHC class II (MHC-II) genes are regulated by an enhanceosome complex containing two gene-specific transcription factors, regulatory factor X complex (RFX) and CIITA. These factors assemble on a strictly conserved regulatory module (S-X-X2-Y) found immediately upstream of the promoters of all classical and nonclassical MHC-II genes as well as the invariant chain (Ii) gene. To identify new targets of RFX and CIITA, we developed a computational approach based on the unique and highly constrained architecture of the composite S-Y motif. We identified six novel S'-Y' modules situated far away from the promoters of known human RFX- and CIITA-controlled genes. Four are situated at strategic positions within the MHC-II locus, and two are found within the Ii gene. These S'-Y' modules function as transcriptional enhancers, are bona fide targets of RFX and CIITA in B cells and IFN-gamma-induced cells, and induce broad domains of histone hyperacetylation. These results reveal a hitherto unexpected level of complexity involving long distance control of MHC-II expression by multiple distal regulatory elements.
Keywords		Acetylation — Acetyltransferases/metabolism — Antigens, Differentiation, B-Lymphocyte/genetics/metabolism — Base Sequence — Cell Line, Tumor — Computational Biology/methods — Conserved Sequence — DNA-Binding Proteins/metabolism/ physiology — Enhancer Elements, Genetic/ physiology — Gene Expression Profiling/methods — Genes, MHC Class II — Genetic Markers/immunology — Histocompatibility Antigens Class II/genetics/metabolism — Histone Acetyltransferases — Histones/metabolism — Humans — Interferon-gamma/physiology — Locus Control Region/ physiology — Molecular Sequence Data — Nuclear Proteins/metabolism/ physiology — Promoter Regions, Genetic — Protein Binding/genetics/immunology — Trans-Activators/metabolism/ physiology — Transcription Factors/metabolism/ physiology
Identifiers		DOI: 10.4049/jimmunol.173.10.6200 PMID: 15528357
Full text		Article - Limited access to UNIGE Other version: http://www.jimmunol.org/cgi/reprint/173/10/6200.pdf
Citation (ISO format)		KRAWCZYK, Michal et al. Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITA. In: Journal of Immunology, 2004, vol. 173, n° 10, p. 6200-6210. https://archive-ouverte.unige.ch/unige:11396