A T lymphocyte-specific transcription complex containing RUNX1 activates MHC class I expression.
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.
Howcroft
T Kevin
TK
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Weissman
Jocelyn D
JD
Gegonne
Anne
A
Singer
Dinah S
DS
D000818:Animals; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
C105242:ALYREF protein, human; D023081:CCAAT-Binding Factor; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors