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.
Highlights
A strong T cell-specific enhancer is located 3' to the human CD2 gene
The results presented here demonstrate that the human T celf-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
Transcription factors with homology to the high mobility group (HMG) of proteins are likely to be important for the T cell specificity of transcription of several genes, such as the CD3E gene [8] and the TcR-a. and -f3 genes [9,10]
Summary
Vol 270, No 13, Issue of March 31, pp. 7515-7522, 1995 Printed in U.S.A. The High Mobility Group Transcription Factor, SOX4, Transactivates the Human CD2 Enhancer*. 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. Studies using transgenic mice have established that a 28.5-kb fragment containing the human CD2 gene carries all of the necessary information for correct tissue-specific expression [2] Within this fragment, a weak promoter together with an enhancer that is located 3' to the gene have been identified [3]. DNase I footprint analysis revealed six protected regions using T cell nuclear extracts [3] Within these regions several close similarities to sequences bound by transcription factors important in T cell- and lymphoid-specific transcription were observed. We demonstrate that members of two transcription factor families which play important roles in T cell transcription, ets, and HMG, bind to cis elements within the CD2 enhancer and that the HMG protein, SOX4, is able to transactivate the CD2 gene
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