The high mobility group transcription factor, SOX4, transactivates the human CD2 enhancer

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• The human CD2 gene has a potent T cell-specific enhancer located 3' to its coding sequence.
• This enhancer contains six distinct regions that bind proteins found in T cell nuclear extracts.
• These binding regions share similarities with known transcription factor binding sites crucial for T cell and lymphoid-specific gene expression.

Purpose of the Study:

• To investigate the transcription factors binding to the human CD2 enhancer.
• To determine the functional role of SOX4 and Elf1 in regulating CD2 gene expression.
• To elucidate the mechanism behind increased CD2 protein expression upon T cell activation.

Main Methods:

• Nuclear protein binding assays using T cell extracts.
• Reporter gene assays to assess transcriptional activation by SOX4.
• Analysis of sequence homology to known transcription factor binding sites.
• Investigation of CD2 protein expression changes post-T cell activation.

Main Results:

• The human T cell-specific transcription factor SOX4 binds to a novel site within the CD2 enhancer, distinct from canonical HMG protein binding sequences.
• SOX4 binding activates reporter gene transcription through tandem copies of this identified sequence.
• The ets-related factor Elf1 binds to an IL-2 NF-AT-like sequence within the enhancer.
• This CD2 NF-AT-like sequence does not confer transcriptional inducibility on a reporter gene.
• Increased CD2 protein expression on the cell surface after T cell activation is a post-transcriptional event.

Conclusions:

• SOX4 plays a role in regulating CD2 gene expression through a novel binding mechanism.
• The CD2 enhancer contains regulatory elements that bind T cell-specific transcription factors.
• CD2 protein upregulation during T cell activation occurs independently of enhancer-driven transcriptional changes.