Cephalic hedgehog expression is regulated directly by Sox17 in endoderm development of Xenopus laevis

Yagi, Yumihiko; Ito, Yuzuru; Kuhara, Satoru; Tashiro, Kosuke

doi:10.1007/s10616-008-9127-2

Cited by 2 publications

(2 citation statements)

References 47 publications

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“…Despite the critical role of Sox17 in endoderm development, only few of its direct transcriptional targets have been identified (e.g. : hnf1b, foxa1 and dhh) (Ahmed et al, 2004;Sinner et al, 2004;Yagi et al, 2008). In Xenopus, ectopic Sox17 is sufficient to initiate endoderm development in pluripotent blastula animal cap cells (Clements et al, 2003;Hudson et al, 1997), and co-injection of stabilized Bcat can enhance this activity (Sinner et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network

Mukherjee

Chaturvedi

Rankin

et al. 2020

eLife

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Lineage specification is governed by gene regulatory networks (GRNs) that integrate the activity of signaling effectors and transcription factors (TFs) on enhancers. Sox17 is a key transcriptional regulator of definitive endoderm development, and yet, its genomic targets remain largely uncharacterized. Here, using genomic approaches and epistasis experiments, we define the Sox17-governed endoderm GRN in Xenopus gastrulae. We show that Sox17 functionally interacts with the canonical Wnt pathway to specify and pattern the endoderm while repressing alternative mesectoderm fates. Sox17 and β-catenin co-occupy hundreds of key enhancers. In some cases, Sox17 and β-catenin synergistically activate transcription apparently independent of Tcfs, whereas on other enhancers, Sox17 represses β-catenin/Tcf-mediated transcription to spatially restrict gene expression domains. Our findings establish Sox17 as a tissue-specific modifier of Wnt responses and point to a novel paradigm where genomic specificity of Wnt/β-catenin transcription is determined through functional interactions between lineage-specific Sox TFs and β-catenin/Tcf transcriptional complexes. Given the ubiquitous nature of Sox TFs and Wnt signaling, this mechanism has important implications across a diverse range of developmental and disease contexts.

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Section: Introductionmentioning

confidence: 99%

Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network

Mukherjee

Chaturvedi

Rankin

et al. 2020

eLife

View full text Add to dashboard Cite

show abstract

“…Despite the critical role of Sox17 in endoderm development, only few of its direct transcriptional target genes have been identified (e.g. : hnf1b, foxa1 and dhh) (Ahmed et al, 2004;Sinner et al, 2004;Yagi et al, 2008). In Xenopus, ectopic Sox17 is sufficient to initiate endoderm development in pluripotent blastula animal cap cells (Clements et al, 2003;Hudson et al, 1997), and co-injection of stabilized Bcat can enhance this activity (Sinner et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endodermal gene regulatory network

Mukherjee

Chaturvedi

Rankin

et al. 2020

Preprint

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Key findings• Sox17 regulates germ layer specification by promoting endoderm differentiation while simultaneously repressing mesectoderm fates.• Functional interactions between Sox17 and Wnt-signaling is a major feature of the GRN controlling endoderm specification and patterning in vivo.• Sox17 and b-catenin co-occupy a subset of enhancers to synergistically stimulate transcription in the absence of Tcfs. • Sox17 regulates the spatial expression domains of Wnt-responsive transcription in the gastrula. ABSTRACT Lineage specification depends on the integration of lineage-determining transcription factors (TFs) and signaling effectors on enhancers to establish gene regulatory networks (GRNs). Sox17 is a key regulator of definitive endoderm development, and yet, its genomic targets remain largely uncharacterized. Here, using genomic approaches and epistasis experiments, we define the Sox17-governed endoderm GRN in Xenopus gastrulae. We show that Sox17 functionally interacts with the canonical Wnt pathway to specify and pattern the endoderm while repressing alternative mesectoderm fates. Together, Sox17 and b-catenin bind hundreds of key enhancers. In some cases, Sox17 and b-catenin synergistically activate transcription in the absence of Tcfs, whereas on other enhancers, Sox17 represses ß-catenin/Tcf-mediated transcription to spatially restrict gene expression domains. Our findings establish Sox17 as a tissue-specific modifier of Wnt responses and point to a novel paradigm where genomic specificity of Wnt/ß-catenin transcription is determined through functional interactions between lineage-specific Sox TFs and ß-catenin/Tcf transcriptional complexes. Given the ubiquitous nature of Sox TFs and Wnt signaling, this could be a general feature of Sox proteins across numerous contexts of development and disease.

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Cephalic hedgehog expression is regulated directly by Sox17 in endoderm development of Xenopus laevis

Cited by 2 publications

References 47 publications

Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network

Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network

Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endodermal gene regulatory network

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