Biology:SOX17

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


SRY-box 17 is a protein that in humans is encoded by the SOX17 gene. [1]

Regulation at the human SOX17 locus

The gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors, located on Chromosome 8 q11.23. It's gene body is isolated within a CTCF loop domain.[2][3][4] Approximately 230 kb upstream of SOX17 it has been identified a tissue specific differentially (hypo-)methylated region (DMR), which consists of SOX17 regulatory elements.[5][6] The DMR in particular bears the most distal definitive endoderm specific enhancer at the SOX17 locus.[7] SOX17 itself has recently been defined as so called topologically insulated gene (TIG). TIGs per definition are single protein coding genes (PCGs) within CTCF loop domains, that are mainly enriched in developmental regulators and suggested to be very tightly controlled via their 3D loop-domain architecture.[8]

Function in development

SOX17 is involved in the regulation of vertebrate embryonic development and in the determination of the endodermal cell fate. The encoded protein acts downstream of TGF beta signaling (Activin) and canonical WNT signaling (Wnt3a).[9][10] Especially the correct phosphorylation of SMAD2/3 within the respective cell cycle (early G1 phase) is crucial for the activation of cardinal endodermal genes (e.g. SOX17) to further enter the definitive endodermal lineage.[11] Besides that, perturbation of the SOX17 centromertic CTCF-boundary in early definitive endoderm differentiation, leads to massive developmental failure and a so called mes-endodermal like trapped cell-state, which can be rescued by ectopic SOX17 expression.[12] In Xenopus gastrulae it has been shown that SOX17 modifies Wnt responses, where genomic specificity of Wnt/β-catenin transcription is determined through functional interactions between SOX17 and β-catenin/Tcf transcriptional complexes.[13]

References

  1. ↑ "Entrez Gene: SRY-box 17". https://www.ncbi.nlm.nih.gov/gene/64321. 
  2. ↑ "Cohesin Loss Eliminates All Loop Domains". Cell 171 (2): 305–320.e24. October 2017. doi:10.1016/j.cell.2017.09.026. PMID 28985562. 
  3. ↑ "Principles of genome folding into topologically associating domains". Science Advances 5 (4): eaaw1668. April 2019. doi:10.1126/sciadv.aaw1668. PMID 30989119. Bibcode: 2019SciA....5.1668S. 
  4. ↑ Wu, Hua-Jun; Landshammer, Alexandro; Stamenova, Elena K.; Bolondi, Adriano; Kretzmer, Helene; Meissner, Alexander; Michor, Franziska (2021-08-12). "Topological isolation of developmental regulators in mammalian genomes" (in en). Nature Communications 12 (1): 4897. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMID 34385432. Bibcode: 2021NatCo..12.4897W. 
  5. ↑ "Transcription factor binding dynamics during human ES cell differentiation". Nature 518 (7539): 344–9. February 2015. doi:10.1038/nature14233. PMID 25693565. Bibcode: 2015Natur.518..344T. 
  6. ↑ Wu, Hua-Jun; Landshammer, Alexandro; Stamenova, Elena K.; Bolondi, Adriano; Kretzmer, Helene; Meissner, Alexander; Michor, Franziska (2021-08-12). "Topological isolation of developmental regulators in mammalian genomes" (in en). Nature Communications 12 (1): 4897. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMID 34385432. Bibcode: 2021NatCo..12.4897W. 
  7. ↑ Wu, Hua-Jun; Landshammer, Alexandro; Stamenova, Elena K.; Bolondi, Adriano; Kretzmer, Helene; Meissner, Alexander; Michor, Franziska (2021-08-12). "Topological isolation of developmental regulators in mammalian genomes" (in en). Nature Communications 12 (1): 4897. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMID 34385432. Bibcode: 2021NatCo..12.4897W. 
  8. ↑ Wu, Hua-Jun; Landshammer, Alexandro; Stamenova, Elena K.; Bolondi, Adriano; Kretzmer, Helene; Meissner, Alexander; Michor, Franziska (2021-08-12). "Topological isolation of developmental regulators in mammalian genomes" (in en). Nature Communications 12 (1): 4897. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMID 34385432. Bibcode: 2021NatCo..12.4897W. 
  9. ↑ "Wnt/β-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse". Development 140 (15): 3128–38. August 2013. doi:10.1242/dev.088765. PMID 23824574. 
  10. ↑ LaBonne, Carole; Morrisey, Edward E, eds (September 2020). "Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network". eLife 9: e58029. doi:10.7554/eLife.58029. PMID 32894225. 
  11. ↑ "The cell-cycle state of stem cells determines cell fate propensity" (in English). Cell 155 (1): 135–47. September 2013. doi:10.1016/j.cell.2013.08.031. PMID 24074866. 
  12. ↑ Wu, Hua-Jun; Landshammer, Alexandro; Stamenova, Elena K.; Bolondi, Adriano; Kretzmer, Helene; Meissner, Alexander; Michor, Franziska (2021-08-12). "Topological isolation of developmental regulators in mammalian genomes" (in en). Nature Communications 12 (1): 4897. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMID 34385432. Bibcode: 2021NatCo..12.4897W. 
  13. ↑ Mukherjee, Shreyasi; Chaturvedi, Praneet; Rankin, Scott A; Fish, Margaret B; Wlizla, Marcin; Paraiso, Kitt D; MacDonald, Melissa; Chen, Xiaoting et al. (2020-09-07). LaBonne, Carole; Morrisey, Edward E. eds. "Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network". eLife 9: e58029. doi:10.7554/eLife.58029. ISSN 2050-084X. PMID 32894225. PMC 7498262. https://doi.org/10.7554/eLife.58029. 

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.





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