Abstract
A strong T cell-specific enhancer is located 3' to the human CD2 gene. Six sequences within this enhancer are bound by proteins present in T cell nuclear extracts. These sequences share homology with sequences bound by several transcription factors involved in T cell- and lymphoid-specific transcription. The results presented here demonstrate that the human T cell-specific transcription factor, SOX4, is able to bind to one of these regions; further, SOX4 transactivates transcription of a reporter gene via three tandem copies of this sequence. The binding of SOX4 to this site is not via a canonical HMG protein binding sequence, identifying a novel class of binding site for this protein. A second sequence within the CD2 enhancer closely resembles the IL-2 NF-AT site. We show that it is bound by the ets-related factor, Elf1. However, unlike the IL-2 NF-AT sequence, the CD2 NF-AT-like sequence is unable to confer transcriptional inducibility on a reporter gene. Consistent with this result, we show that the observed increase in expression of CD2 protein on the cell surface following T cell activation is a post-transcriptional event.
MeSH terms
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Antigens, CD / biosynthesis
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Antigens, CD / genetics
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Base Sequence
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Blotting, Northern
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CD2 Antigens / biosynthesis*
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CD2 Antigens / genetics*
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Cell Nucleus / metabolism
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Chloramphenicol O-Acetyltransferase / biosynthesis
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Cloning, Molecular
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Consensus Sequence
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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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High Mobility Group Proteins / metabolism*
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Humans
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Immunophenotyping
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Interleukin-2 / biosynthesis
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Interleukin-2 / genetics
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Luciferases / biosynthesis
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Molecular Sequence Data
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Mutagenesis
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NFATC Transcription Factors
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Nuclear Proteins*
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Recombinant Fusion Proteins / biosynthesis
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SOXC Transcription Factors
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Sequence Deletion
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Sequence Homology, Nucleic Acid
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T-Lymphocytes / immunology
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Trans-Activators / metabolism*
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Transcription Factors / metabolism
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Transcription, Genetic
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Transfection
Substances
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Antigens, CD
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CD2 Antigens
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DNA-Binding Proteins
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High Mobility Group Proteins
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Interleukin-2
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NFATC Transcription Factors
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Nuclear Proteins
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Recombinant Fusion Proteins
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SOX4 protein, human
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SOXC Transcription Factors
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Trans-Activators
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Transcription Factors
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Luciferases
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Chloramphenicol O-Acetyltransferase