The High Mobility Group Transcription Factor, SOX4, Transactivates the Human CD2 Enhancer (*)
- From the (1)Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom, St. Mary's Hospital Medical School, Department of Immunology, Norfolk Place, London W2 1PG, United Kingdom, and
- (2)University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH, United Kingdom
- ¶ To whom correspondence should be addressed. Tel.: 44-71-269-3069; Fax: 44-71-269-3479.
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.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- LCR
-
locus control region
- TcR
-
T cell receptor
- HMG
-
high mobility group
- EMSA
-
electrophoretic mobility shift analysis
- GST
-
glutathione S-transferase
- IPTG
-
isopropyl-1-thio-β-D-galactopyranoside
- PAGE
-
polyacrylamide gel electrophoresis
- HA
-
hemagglutinin
- PMA
-
phorbol 12-myristate 13-acetate
- SEB
-
staphylococcal enterotoxin B
- TNF
-
tissue necrosis factor
- TCF
-
T cell transcription factor
- IL
-
interleukin
- CAT
-
chloramphenicol acetyltransferase
- kb
-
kilobase(s)
- CRE
-
cyclic AMP response element.
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- Received September 16, 1994.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
