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

doi:10.4049/jimmunol.173.10.6200

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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		The 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: The Journal of immunology, 2004, vol. 173, n° 10, p. 6200-6210. doi: 10.4049/jimmunol.173.10.6200 https://archive-ouverte.unige.ch/unige:11396