SRY-box 17 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the SOX17
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
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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. Approximately 230 kb upstream of ''SOX17'' it has been identified a tissue specific differentially (hypo-)methylated region (DMR), which consists of ''SOX17'' regulatory elements. The DMR in particular bears the most distal definitive endoderm specific enhancer at the ''SOX17'' locus. ''SOX17'' itself has recently been defined as so called topologically insulated gene (TIG). TIGs per definition are single protein coding genes (PCGs) within
CTCF
Transcriptional repressor CTCF also known as 11-zinc finger protein or CCCTC-binding factor is a transcription factor that in humans is encoded by the ''CTCF'' gene. CTCF is involved in many cellular processes, including transcriptional regulatio ...
loop domains, that are mainly enriched in developmental regulators and suggested to be very tightly controlled via their 3D loop-domain architecture.
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). 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. Besides that, perturbation of the ''SOX17'' centromertic
CTCF
Transcriptional repressor CTCF also known as 11-zinc finger protein or CCCTC-binding factor is a transcription factor that in humans is encoded by the ''CTCF'' gene. CTCF is involved in many cellular processes, including transcriptional regulatio ...
-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. 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.
References
Further reading
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* MacCarthy CM, Malik V, Wu G, et al., & Velychko S (September 2022)
"Enhancing Sox/Oct cooperativity induces higher-grade developmental reset" bioRxiv.
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