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Functional diversity of human basic helix-loop-helix transcription factor TCF4 isoforms generated by alternative 5'
Mari Sepp1, Kaja Kannike, Ave Eesmaa
1Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
Plos One
|July 27, 2011
Summary
The human TCF4 gene shows varied expression across tissues, with high levels in the brain. Alternative splicing generates diverse TCF4 protein isoforms with distinct functions and cellular distributions.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- Transcription Factor 4 (TCF4) is a basic helix-loop-helix protein binding E-box DNA sequences.
- TCF4 plays roles in various cell types, with recent focus on the nervous system.
- The human TCF4 gene is linked to schizophrenia and Pitt-Hopkins syndrome, but its detailed structure and expression are unknown.
Purpose of the Study:
- To characterize the structure and expression of the human TCF4 gene.
- To investigate the coding potential and functional diversity of TCF4 protein isoforms.
Main Methods:
- Analysis of human tissue samples for TCF4 gene structure and expression at mRNA and protein levels.
- Overexpression of individual TCF4 isoforms in cultured human cells.
- Reporter gene assays to assess transcriptional activity of TCF4 isoforms.
Main Results:
- Human TCF4 mRNA is widely expressed, with particularly high levels in the brain.
- Numerous 5' and alternative internal exons generate TCF4 protein isoforms with 18 different N-termini.
- TCF4 isoform distribution is differentially regulated, some exclusively nuclear, others dependent on partners.
- TCF4 isoforms exhibit varied transcriptional activity based on the presence and combination of their two activation domains.
Conclusions:
- The study details inter-tissue variability in human TCF4 expression.
- Evidence for functional diversity among alternative TCF4 protein isoforms is provided.
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