Abstract
CD1 molecules are MHC class I-like glycoproteins specialized in presenting lipid/glycolipid Ags to T cells. The distinct cell-type specific expression of CD1D1 plays an important role in the development and function of NKT cells, a unique subset of immunoregulatory T cells. However, the mechanisms regulating CD1D1 expression are largely unknown. In this study, we have characterized the upstream region of the CD1D1 gene and identified a minimal promoter region within 200 bp from the translational start site of CD1D1 that exhibits cell-type specific promoter activity. Analysis of this region revealed an Ets binding site critical for CD1D1 promoter activity. Gel shift assays and chromatin immunoprecipitation experiments showed that Elf-1 and PU.1 bind to the CD1D1 promoter. Furthermore, we found that gene disruption of Elf-1 resulted in decreased CD1D1 expression on B cells but not other cell types, whereas conditional activation of PU.1 negatively regulated CD1D1 expression in PU.1-deficient myeloid cells. These findings are the first to demonstrate that Ets proteins are involved in the transcriptional regulation of CD1D1 and that they may function uniquely in different cell types.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD1 / biosynthesis
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Antigens, CD1 / genetics*
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Antigens, CD1 / metabolism*
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Antigens, CD1d
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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Base Sequence
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Binding Sites / genetics
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Cell Line
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Cell Line, Tumor
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Cell Membrane / genetics
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Consensus Sequence
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Down-Regulation / genetics
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Down-Regulation / immunology
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Ephrin-A2 / genetics
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Ephrin-A2 / metabolism
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Gene Expression Regulation, Neoplastic* / immunology
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Leukemia P388 / genetics
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Leukemia P388 / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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Oligonucleotide Array Sequence Analysis
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Promoter Regions, Genetic / immunology
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-ets
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RNA, Messenger / biosynthesis
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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Trans-Activators / deficiency
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / physiology*
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Transcription Initiation Site
Substances
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Antigens, CD1
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Antigens, CD1d
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Ephrin-A2
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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RNA, Messenger
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Trans-Activators
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Transcription Factors
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proto-oncogene protein Spi-1