|Title||Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITA.|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Krawczyk M, Peyraud N, Rybtsova N, Masternak K, Bucher P, le Barras E, Reith W|
|Date Published||2004 Nov 15|
|Keywords||Acetylation, Acetyltransferases, Antigens, Differentiation, B-Lymphocyte, Base Sequence, Cell Line, Tumor, Computational Biology, Conserved Sequence, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Profiling, Genes, MHC Class II, Genetic Markers, Histocompatibility Antigens Class II, Histone Acetyltransferases, Histones, Humans, Interferon-gamma, Locus Control Region, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Trans-Activators, Transcription Factors|
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.
|Alternate Journal||J. Immunol.|