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Published on: June 24, 2021
Comparative genomics on SFRP1 orthologs
1M&M Medical BioInformatics, Hongo 113-0033, Japan.
Abstract:
SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, WIF1, DKK1, DKK2, DKK3, DKK4 are secreted-type WNT signaling modulators. SFRP1 tumor suppressor gene at human chromosome 8p11.21 is inactivated in colorectal cancer and other tumors by deletion and by epigenetic CpG hypermethylation. Here, we identified and characterized the rat Sfrp1 gene by using bioinformatics. Rat Sfrp1 gene, consisting of three exons, was located within AC112899.4 genome sequence. Complete coding sequence of rat Sfrp1 was determined by assembling AC112899.4 genome sequence, CK838748 EST, and BF417482 EST. Rat Sfrp1 (314 aa) consisted of a signal peptide (codon 1-31), Frizzled domain with ten conserved Cys residues (codon 49-168), and Netrin (NTR) domain with six conserved Cys residues (codon 186-314). Rat Sfrp1 showed 98.7%, 95.2%, 94.3%, 82.5% and 58.3% total-amino-acid identity with mouse Sfrp1, human SFRP1, cow Sfrp1, chicken sfrp1 and zebrafish sfrp1, respectively. SFRP1 mRNA was expressed in embryonic stem (ES) cells, neuroblastoma, liver adeno-carcinoma, and skin squamous cell carcinoma. Match program revealed that AP1, COMP1, and double ETS1-binding sites were conserved between human SFRP1 and rat Sfrp1 promoters. This is the first report on comparative integromics analyses on Sfrp1 orthologs.
Insights
The rat Sfrp1 gene, a key WNT signaling modulator, was identified and characterized. This study provides the first comparative analysis of Sfrp1 orthologs, revealing conserved regulatory elements and high sequence identity with other species.
Area of Science:
- Genetics
- Molecular Biology
- Bioinformatics
Background:
- Secreted-type WNT signaling modulators, including SFRP1, play critical roles in cellular processes.
- SFRP1 functions as a tumor suppressor gene, frequently inactivated in various cancers.
- Understanding Sfrp1 orthologs is crucial for cancer research and therapeutic development.
Purpose of the Study:
- To identify and characterize the rat Sfrp1 gene.
- To perform comparative integromics analyses of Sfrp1 orthologs across species.
- To investigate the conserved regulatory elements in Sfrp1 promoters.
Main Methods:
- Bioinformatic analysis of genomic and EST sequences to identify and assemble the rat Sfrp1 gene.
- Amino acid sequence analysis to determine protein domains and conserved residues.
- Comparative sequence analysis to assess homology with Sfrp1 orthologs from other species.
- Promoter analysis using the Match program to identify conserved transcription factor binding sites.
Main Results:
- The rat Sfrp1 gene was identified and its complete coding sequence determined.
- Rat Sfrp1 (314 aa) comprises a signal peptide, Frizzled domain, and Netrin domain.
- High amino acid identity was observed between rat Sfrp1 and orthologs in mouse (98.7%) and human (95.2%).
- Conserved AP1, COMP1, and ETS1 binding sites were identified in the promoter regions of human SFRP1 and rat Sfrp1.
Conclusions:
- This study provides the first comprehensive characterization of the rat Sfrp1 gene and its comparative analysis with orthologs.
- The identified conserved features suggest functional importance of Sfrp1 across species.
- Findings contribute to understanding WNT signaling pathway regulation and potential therapeutic targets in cancer.
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