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Published on: November 29, 2016
Comparative genomics on SOX2 orthologs
1M&M Medical BioInformatics, Hongo 113-0033, Japan.
Abstract:
SOX2 and POU5F1 (OCT3 or OCT4) transcription factors are implicated in FGF4 expression in embryonic stem (ES) cells. SOX2, POU5F1, and FGF4 are key molecules for the integrome network in oncology and stem cell biology. SOX2 gene at human chromosome 3q26.33, SOX1 gene at 13q34, and SOX3 gene at Xq27.1 constitute a subfamily among the SOX gene family. Here, rat Sox2 and Xenopus sox2 genes were identified and characterized by using bioinformatics for comparative genomics and comparative proteomics analyses. Rat Sox2 gene, encoding a 319-aa protein, was located around the nucleotide position 73213-75621 of rat genome sequence AC123231.4. Xenopus tropicalis sox2 complete coding sequence, encoding a 311-aa protein, was derived from CR760314.1 cDNA. Rat Sox2 showed 98.4%, 97.8%, 92.2%, 88.1% and 86.8% total amino-acid identity with mouse Sox2, human SOX2, chicken sox2, Xenopus sox2 and zebrafish sox2, respectively. SOX123C domain was identified as the novel domain corresponding to the C-terminal region conserved among SOX1, SOX2 and SOX3 orthologs. Vertebrate SOX1, SOX2 and SOX3 orthologs were found consisting of HMG box and SOX123C domain. SOX9, TCF/LEF, POU2F1 and COMP1 binding sites were conserved among human SOX2 promoter, rat Sox2 promoter, and mouse Sox2 promoter. SOX2 mRNA was expressed in ES cells, fetal brain, anaplastic oligodendroglioma, rhabdomyosarcoma, and small cell lung carcinoma. Due to the pivotal role of SOX2 in the early embryogenesis, SOX2 promoter and SOX2 protein were well conserved during vertebrate evolution. This is the first report on comparative integromics analyses on the SOX2 orthologs.
Insights
SOX2 and POU5F1 (OCT3 or OCT4) are key transcription factors in embryonic stem cells. Comparative genomics and proteomics reveal conserved SOX2 protein domains and regulatory elements across vertebrates, highlighting its evolutionary importance.
Area of Science:
- Stem cell biology
- Genomics
- Proteomics
- Evolutionary biology
Background:
- SOX2 and POU5F1 (OCT3 or OCT4) transcription factors regulate FGF4 expression in embryonic stem (ES) cells.
- SOX2, POU5F1, and FGF4 are crucial for the integrome network in oncology and stem cell biology.
- The SOX gene family includes SOX2, SOX1, and SOX3, forming a distinct subfamily.
Purpose of the Study:
- To identify and characterize rat Sox2 and Xenopus sox2 genes using bioinformatics.
- To perform comparative genomics and proteomics analyses on SOX2 orthologs.
- To investigate the evolutionary conservation of SOX2 and its regulatory elements.
Main Methods:
- Bioinformatics analysis of rat and Xenopus sox2 genes.
- Comparative genomics and proteomics for amino-acid identity and domain analysis.
- Identification and comparison of conserved transcription factor binding sites in SOX2 promoters.
Main Results:
- Rat Sox2 gene encodes a 319-aa protein; Xenopus tropicalis sox2 encodes a 311-aa protein.
- High amino-acid identity observed between rat Sox2 and orthologs from mouse, human, chicken, Xenopus, and zebrafish.
- A novel SOX123C domain was identified, conserved in vertebrate SOX1, SOX2, and SOX3 orthologs, alongside the HMG box.
- Conserved SOX9, TCF/LEF, POU2F1, and COMP1 binding sites were found in human, rat, and mouse SOX2 promoters.
- SOX2 mRNA expression detected in ES cells, fetal brain, and various tumors.
Conclusions:
- SOX2 protein and its promoter are highly conserved during vertebrate evolution due to its role in early embryogenesis.
- Comparative integromics analyses reveal conserved domains and regulatory elements in SOX2 orthologs.
- SOX2 plays a pivotal role in stem cell biology and is implicated in various cancers.
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