A gene regulatory program controlling early Xenopus mesendoderm formation: Network conservation and motifs

Charney, Rebekah M.; Paraiso, Kitt D.; Blitz, Ira L.; Cho, Ken W.Y.

doi:10.1016/j.semcdb.2017.03.003

Cited by 42 publications

(57 citation statements)

References 207 publications

(188 reference statements)

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“…Together with previous work (Charney et al, 2017b;Zorn and Wells, 2009), this suggests that Sox17 and the other core endoderm TFs interact with Wnt and Nodal in a series of positive and negative feedback loops to control germ layer segregation and modulate spatial gene expression.…”

Section: The Sox17-bcat Regulated Endodermal Grnsupporting

confidence: 65%

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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Section: The Sox17-bcat Regulated Endodermal Grnsupporting

confidence: 65%

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

Mukherjee

Chaturvedi

Rankin

et al. 2020

Preprint

Self Cite

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“…However, as suggested earlier, a host of other transcription factors is required for proper development of neural crest cells. Unlike other cell fates such as endoderm (Charney, Paraiso, Blitz, & Cho, ) and hematopoietic stem cells (Swiers, Patient, & Loose, ), the neural crest field is still relatively new in terms of the identity of regulatory factors involved in neural crest formation, and the GRN through which they function. However, in the past two decades, a large number of transcription factors have been identified to play a role in regulating different stages of neural crest formation.…”

Section: Transcriptional Network Underlying Neural Crest Cell Formationmentioning

confidence: 99%

Specification and formation of the neural crest: Perspectives on lineage segregation

Prasad

Charney

Garcı́a-Castro

2019

Genesis

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Summary The neural crest is a fascinating embryonic population unique to vertebrates that is endowed with remarkable differentiation capacity. Thought to originate from ectodermal tissue, neural crest cells generate neurons and glia of the peripheral nervous system, and melanocytes throughout the body. However, the neural crest also generates many ectomesenchymal derivatives in the cranial region, including cell types considered to be of mesodermal origin such as cartilage, bone, and adipose tissue. These ectomesenchymal derivatives play a critical role in the formation of the vertebrate head, and are thought to be a key attribute at the center of vertebrate evolution and diversity. Further, aberrant neural crest cell development and differentiation is the root cause of many human pathologies, including cancers, rare syndromes, and birth malformations. In this review, we discuss the current findings of neural crest cell ontogeny, and consider tissue, cell, and molecular contributions toward neural crest formation. We further provide current perspectives into the molecular network involved during the segregation of the neural crest lineage.

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“…An important goal of developmental biology is to elucidate how signaling effectors and TFs interact on distinct sets of CRMs within the chromatin landscape to form gene regulatory networks (GRNs) that activate lineage-specific transcriptional programs whilst repressing expression of alternative fates (Charney et al, 2017b). This will provide a deeper understanding of how transcriptional networks are established, dysregulated in disease, and how GRNs might be manipulated for therapeutic purposes.…”

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.

show abstract

A gene regulatory program controlling early Xenopus mesendoderm formation: Network conservation and motifs

Cited by 42 publications

References 207 publications

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

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

Specification and formation of the neural crest: Perspectives on lineage segregation

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

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