Abstract
In vivo, a wild-type pattern of major histocompatibility complex (MHC) class II expression requires a locus control region (LCR). Whereas the role of promoter-proximal MHC class II regulatory sequences is well established, the function of the distal LCR remained obscure. We show here that this LCR is bound by the MHC class II-specific transactivators regulatory factor X (RFX) and class II transactivator (CIITA). Binding of these factors induces long-range histone acetylation, RNA polymerase II recruitment and the synthesis of extragenic transcripts within the LCR. The finding that RFX and CIITA regulate the function of the MHC class II LCR reveals an unexpected degree of complexity in the mechanisms controlling MHC class II gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Binding Sites / genetics
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Cell Line
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Chromatin / genetics*
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Chromatin / metabolism
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DNA-Binding Proteins / metabolism
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Enhancer Elements, Genetic
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Gene Expression Regulation
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Genes, MHC Class II*
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HLA-DR Antigens / genetics
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HLA-DR alpha-Chains
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Humans
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Locus Control Region*
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Mice
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Nuclear Proteins*
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RNA Polymerase II / metabolism
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Regulatory Factor X Transcription Factors
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Trans-Activators / metabolism
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Transcription Factors / metabolism
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Transcription, Genetic
Substances
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Chromatin
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DNA-Binding Proteins
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HLA-DR Antigens
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HLA-DR alpha-Chains
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MHC class II transactivator protein
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Nuclear Proteins
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Regulatory Factor X Transcription Factors
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Trans-Activators
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Transcription Factors
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RNA Polymerase II