PMID:22265740

Citation	Fong, H, Wong, RC and Donovan, PJ (2012) Transcriptional regulation of TRKC by SOX2 in human embryonic stem cells. Stem Cell Res 8:206-14
Abstract	Human embryonic stem (hES) cells have the dual ability to self-renew and differentiate into specialized cell types. However, in order to realize the full potential of these cells it is important to understand how the genes responsible for their unique characteristics are regulated. In this study we examine the regulation of the tropomyosin-related kinase (TRK) genes which encode for receptors important in hES cell survival and self-renewal. Although the TRK genes have been studied in many neuronal cell types, the regulation of these genes in hES cells is unclear. Our study demonstrates a novel regulatory relationship between the TRKC gene and the transcription factor SOX2. Our results found that hES cells highly express full-length and truncated forms of the TRKC gene. However, examination of the related TRKB gene showed a lower overall expression of both full-length and truncated forms. Through RNA interference, we knocked down expression levels of SOX2 in hES cells and examined the expression of TRKC, as well as TRKB. Upon loss of SOX2 we found that TRKC mRNA levels were significantly downregulated but TRKB levels remained unchanged, demonstrating an important regulatory dependence on SOX2 by TRKC. We also found that TRKC protein levels were also decreased after SOX2 knock down. Further analysis found the regulatory region of TRKC to be highly conserved among many mammals with potential SOX binding motifs. We confirmed a specific binding motif as a site that SOX2 utilizes to directly interact with the TRKC regulatory region. In addition, we found that SOX2 drives expression of the TRKC gene by activating a luciferase reporter construct containing the TRKC regulatory region and the SOX binding motif.
Links	PubMed Online version:10.1016/j.scr.2011.10.003
Keywords	Alternative Splicing/genetics; Animals; Base Sequence; Binding Sites; Conserved Sequence/genetics; Down-Regulation/genetics; Embryonic Stem Cells/enzymology; Gene Expression Regulation, Enzymologic; Gene Knockdown Techniques; Genes, Reporter/genetics; Humans; Mammals/genetics; Molecular Sequence Data; Promoter Regions, Genetic/genetics; Protein Binding/genetics; Receptor, trkC/genetics; Receptor, trkC/metabolism; SOXB1 Transcription Factors/metabolism; Transcription, Genetic
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:SOX2		GO:0045289: luciferin monooxygenase activity	ECO:0000314:		F		In figure 6 B Co-transfection of the SOX2 overexpression vector with the TRKC-LUC Site A + B reporter resulted in a 2.0-fold increase in luciferase activity compared to cells transfected with the empty overexpression vector	complete CACAO 5071

References

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