Article: article from journal or magazin.
Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITA.
Journal of Immunology
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.
Acetylation, Acetyltransferases/metabolism, Antigens, Differentiation, B-Lymphocyte/genetics, Antigens, Differentiation, B-Lymphocyte/metabolism, Base Sequence, Cell Line, Tumor, Computational Biology/methods, Conserved Sequence, DNA-Binding Proteins/metabolism, DNA-Binding Proteins/physiology, Enhancer Elements, Genetic/physiology, Gene Expression Profiling/methods, Genes, MHC Class II, Genetic Markers/immunology, Histocompatibility Antigens Class II/genetics, Histocompatibility Antigens Class II/metabolism, Histone Acetyltransferases, Histones/metabolism, Humans, Interferon-gamma/physiology, Locus Control Region/physiology, Molecular Sequence Data, Nuclear Proteins/metabolism, Nuclear Proteins/physiology, Promoter Regions, Genetic, Protein Binding/genetics, Protein Binding/immunology, Trans-Activators/metabolism, Trans-Activators/physiology, Transcription Factors/metabolism, Transcription Factors/physiology
Web of science
Last modification date