SOX17
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSOX17, VUR3, SRY-box 17, SRY-box transcription factor 17
External IDsOMIM: 610928 MGI: 107543 HomoloGene: 7948 GeneCards: SOX17
Orthologs
SpeciesHumanMouse
Entrez

64321

20671

Ensembl

ENSG00000164736

ENSMUSG00000025902

UniProt

Q9H6I2

Q61473

RefSeq (mRNA)

NM_022454

NM_001289464
NM_001289465
NM_001289466
NM_001289467
NM_011441

RefSeq (protein)

NP_071899

NP_001276393
NP_001276394
NP_001276395
NP_001276396
NP_035571

Location (UCSC)Chr 8: 54.46 – 54.46 MbChr 1: 4.56 – 4.57 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

SRY-box 17 is a protein that in humans is encoded by the SOX17 gene. [5]

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. Its gene body is isolated within a CTCF loop domain.[6][7][8] Approximately 230 kb upstream of SOX17 it has been identified a tissue specific differentially (hypo-)methylated region (DMR), which consists of SOX17 regulatory elements.[9][10] The DMR in particular bears the most distal definitive endoderm specific enhancer at the SOX17 locus.[11] 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.[12]

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).[13][14] 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.[15] 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.[16] 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.[17]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000164736 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025902 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: SRY-box 17". Retrieved 2017-09-07.
  6. ↑ Rao SS, Huang SC, Glenn St Hilaire B, Engreitz JM, Perez EM, Kieffer-Kwon KR, et al. (October 2017). "Cohesin Loss Eliminates All Loop Domains". Cell. 171 (2): 305–320.e24. doi:10.1016/j.cell.2017.09.026. hdl:1721.1/118942. PMC 5846482. PMID 28985562.
  7. ↑ Szabo Q, Bantignies F, Cavalli G (April 2019). "Principles of genome folding into topologically associating domains". Science Advances. 5 (4): eaaw1668. Bibcode:2019SciA....5.1668S. doi:10.1126/sciadv.aaw1668. PMC 6457944. PMID 30989119.
  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". Nature Communications. 12 (1): 4897. Bibcode:2021NatCo..12.4897W. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMC 8361032. PMID 34385432.
  9. ↑ Tsankov AM, Gu H, Akopian V, Ziller MJ, Donaghey J, Amit I, et al. (February 2015). "Transcription factor binding dynamics during human ES cell differentiation". Nature. 518 (7539): 344–9. Bibcode:2015Natur.518..344T. doi:10.1038/nature14233. PMC 4499331. PMID 25693565.
  10. ↑ 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". Nature Communications. 12 (1): 4897. Bibcode:2021NatCo..12.4897W. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMC 8361032. PMID 34385432.
  11. ↑ 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". Nature Communications. 12 (1): 4897. Bibcode:2021NatCo..12.4897W. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMC 8361032. PMID 34385432.
  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". Nature Communications. 12 (1): 4897. Bibcode:2021NatCo..12.4897W. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMC 8361032. PMID 34385432.
  13. ↑ Engert S, Burtscher I, Liao WP, Dulev S, Schotta G, Lickert H (August 2013). "Wnt/β-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse". Development. 140 (15): 3128–38. doi:10.1242/dev.088765. PMID 23824574.
  14. ↑ Mukherjee S, Chaturvedi P, Rankin SA, Fish MB, Wlizla M, Paraiso KD, et al. (September 2020). LaBonne C, Morrisey EE (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. PMC 7498262. PMID 32894225.
  15. ↑ Pauklin S, Vallier L (September 2013). "The cell-cycle state of stem cells determines cell fate propensity". Cell. 155 (1): 135–47. doi:10.1016/j.cell.2013.08.031. PMC 3898746. PMID 24074866.
  16. ↑ 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". Nature Communications. 12 (1): 4897. Bibcode:2021NatCo..12.4897W. doi:10.1038/s41467-021-24951-7. ISSN 2041-1723. PMC 8361032. PMID 34385432.
  17. ↑ Mukherjee, Shreyasi; Chaturvedi, Praneet; Rankin, Scott A; Fish, Margaret B; Wlizla, Marcin; Paraiso, Kitt D; MacDonald, Melissa; Chen, Xiaoting; Weirauch, Matthew T; Blitz, Ira L; Cho, Ken WY (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. PMC 7498262. PMID 32894225.

Further reading

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


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