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