Abstract
MHC class I expression is subject to both tissue-specific and hormonal regulatory mechanisms. Consequently, levels of expression vary widely among tissues, with the highest levels of class I occurring in the lymphoid compartment, in T cells and B cells. Although the high class I expression in B cells is known to involve the B cell enhanceosome, the molecular basis for high constitutive class I expression in T cells has not been explored. T cell-specific genes, such as TCR genes, are regulated by a T cell enhanceosome consisting of RUNX1, CBFbeta, LEF1, and Aly. In this report, we demonstrate that MHC class I gene expression is enhanced by the T cell enhanceosome and results from a direct interaction of the RUNX1-containing complex with the class I gene in vivo. T cell enhanceosome activation of class I transcription is synergistic with CIITA-mediated activation and targets response elements distinct from those targeted by CIITA. These findings provide a molecular basis for the high levels of MHC class I in T cells.
MeSH terms
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Animals
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CCAAT-Binding Factor / genetics
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CCAAT-Binding Factor / metabolism
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Core Binding Factor Alpha 2 Subunit
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Enhancer Elements, Genetic / immunology*
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / physiology*
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Gene Expression Regulation / immunology*
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HeLa Cells
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Histocompatibility Antigens Class I / biosynthesis*
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Histocompatibility Antigens Class I / genetics*
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Humans
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Jurkat Cells
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Lymphoid Enhancer-Binding Factor 1
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Promoter Regions, Genetic / immunology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Transfection
Substances
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ALYREF protein, human
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CCAAT-Binding Factor
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Core Binding Factor Alpha 2 Subunit
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DNA-Binding Proteins
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class I
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LEF1 protein, human
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Lef1 protein, mouse
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Lymphoid Enhancer-Binding Factor 1
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MHC class II transactivator protein
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Nuclear Proteins
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Proto-Oncogene Proteins
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RNA-Binding Proteins
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RUNX1 protein, human
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Runx1 protein, mouse
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Trans-Activators
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Transcription Factors