SOX17

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

SOX17
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2YUL, 4A3N
Identifiers
Aliases	SOX17, VUR3, SRY-box 17, SRY-box transcription factor 17
External IDs	OMIM: 610928; MGI: 107543; HomoloGene: 7948; GeneCards: SOX17; OMA:SOX17 - orthologs
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8q11.23 Start 54,457,935 bp[1] End 54,460,892 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 A1|1 1.65 cM Start 4,561,154 bp[2] End 4,567,577 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell pericardium endometrium right uterine tube vena cava gonad left uterine tube tibial nerve subcutaneous adipose tissue muscle of thigh Top expressed in left lung lobe gastrula external carotid artery primitive streak internal carotid artery right lung right lung lobe uterus carotid body substantia nigra More reference expression data BioGPS n/a
Gene ontology Molecular function sequence-specific DNA binding DNA binding beta-catenin binding DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific transcription coactivator activity transcription factor binding protein binding protein heterodimerization activity transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component transcription regulator complex nucleoplasm nucleus Biological process renal system development endoderm development regulation of embryonic development regulation of transcription, DNA-templated positive regulation of protein catabolic process stem cell fate specification positive regulation of skeletal muscle tissue development embryonic foregut morphogenesis embryonic organ development endodermal digestive tract morphogenesis negative regulation of mesodermal cell fate specification inner cell mass cellular morphogenesis negative regulation of Wnt signaling pathway protein stabilization endocardium formation outflow tract morphogenesis signal transduction involved in regulation of gene expression endodermal cell fate determination mRNA transcription by RNA polymerase II regulation of mesodermal cell fate specification negative regulation of transcription by RNA polymerase II Wnt signaling pathway endocardial cell differentiation regulation of cardiac cell fate specification transcription, DNA-templated stem cell differentiation embryonic heart tube development vasculogenesis positive regulation of transcription, DNA-templated heart looping cardiac cell fate determination common bile duct development negative regulation of Wnt signaling pathway involved in heart development rostrocaudal neural tube patterning positive regulation of gene expression cardiogenic plate morphogenesis heart formation embryonic heart tube morphogenesis negative regulation of cell growth protein destabilization angiogenesis spermatogenesis positive regulation of cell differentiation regulation of stem cell division gastrulation gall bladder development canonical Wnt signaling pathway regulation of cell differentiation cell migration involved in gastrulation endoderm formation regulation of stem cell proliferation negative regulation of canonical Wnt signaling pathway positive regulation of transcription by RNA polymerase II cellular response to leukemia inhibitory factor cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 1: 4.56 – 4.57 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. GRCh38: Ensembl release 89: ENSG00000164736 – Ensembl, May 2017
2. 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

• Zhang W, Glöckner SC, Guo M, Machida EO, Wang DH, Easwaran H, et al. (April 2008). "Epigenetic inactivation of the canonical Wnt antagonist SRY-box containing gene 17 in colorectal cancer". Cancer Research. 68 (8): 2764–72. doi:10.1158/0008-5472.CAN-07-6349. PMC 2823123. PMID 18413743.
• Patterson ES, Addis RC, Shamblott MJ, Gearhart JD (August 2008). "SOX17 directly activates Zfp202 transcription during in vitro endoderm differentiation". Physiological Genomics. 34 (3): 277–84. doi:10.1152/physiolgenomics.90236.2008. PMID 18523156.
• Ferrell RE, Kimak MA, Lawrence EC, Finegold DN (2008). "Candidate gene analysis in primary lymphedema". Lymphatic Research and Biology. 6 (2): 69–76. doi:10.1089/lrb.2007.1022. PMID 18564921.
• Séguin CA, Draper JS, Nagy A, Rossant J (August 2008). "Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells". Cell Stem Cell. 3 (2): 182–95. doi:10.1016/j.stem.2008.06.018. PMID 18682240.
• Semb H (October 2008). "Expandable endodermal progenitors: new tools to explore endoderm and its derivatives". Cell Stem Cell. 3 (4): 355–6. doi:10.1016/j.stem.2008.09.010. PMID 18940723.
• Fu DY, Wang ZM, Wang BL, Shen ZZ, Huang W, Shao ZM (February 2010). "Sox17, the canonical Wnt antagonist, is epigenetically inactivated by promoter methylation in human breast cancer". Breast Cancer Research and Treatment. 119 (3): 601–12. doi:10.1007/s10549-009-0339-8. PMID 19301122. S2CID 8614063.
• Nonaka D (May 2009). "Differential expression of SOX2 and SOX17 in testicular germ cell tumors". American Journal of Clinical Pathology. 131 (5): 731–6. doi:10.1309/AJCP7MNCNBCRN8NO. PMID 19369635.
• Du YC, Oshima H, Oguma K, Kitamura T, Itadani H, Fujimura T, et al. (October 2009). "Induction and down-regulation of Sox17 and its possible roles during the course of gastrointestinal tumorigenesis". Gastroenterology. 137 (4): 1346–57. doi:10.1053/j.gastro.2009.06.041. hdl:2297/25144. PMID 19549530. S2CID 6296792.
• Stefanovic S, Abboud N, Désilets S, Nury D, Cowan C, Pucéat M (September 2009). "Interplay of Oct4 with Sox2 and Sox17: a molecular switch from stem cell pluripotency to specifying a cardiac fate". The Journal of Cell Biology. 186 (5): 665–73. doi:10.1083/jcb.200901040. PMC 2742180. PMID 19736317.
• MacCarthy CM, Malik V, Wu G, et al., & Velychko S (September 2022). "Enhancing Sox/Oct cooperativity induces higher-grade developmental reset". bioRxiv. doi:10.1101/2022.09.23.509242

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