Analysis of the <i>Tcf‐3</i> promoter during early development of <i>Xenopus</i>

Spieker, Nicole; Peterson, Josi; Reneman, Stefan; Destrée, Olivier

doi:10.1002/dvdy.20150

Cited by 5 publications

(6 citation statements)

References 26 publications

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“…This indicates that DNA methylation may play a role in the regulation of Tcf3 expression [32]. To test whether the observed Tcf3 down-regulation in Apc NN ESCs results from DNA methylation, we employed the bisulfite-conversion method followed by sequencing and methylation-specific PCR to analyze the Tcf3 promoter in Apc NN cells and compare its methylation pattern to wild type ESCs.…”

Section: Resultsmentioning

confidence: 99%

Wnt Signaling Regulates the Lineage Differentiation Potential of Mouse Embryonic Stem Cells through Tcf3 Down-Regulation

et al. 2013

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Canonical Wnt signaling plays a rate-limiting role in regulating self-renewal and differentiation in mouse embryonic stem cells (ESCs). We have previously shown that mutation in the Apc (adenomatous polyposis coli) tumor suppressor gene constitutively activates Wnt signaling in ESCs and inhibits their capacity to differentiate towards ecto-, meso-, and endodermal lineages. However, the underlying molecular and cellular mechanisms through which Wnt regulates lineage differentiation in mouse ESCs remain to date largely unknown. To this aim, we have derived and studied the gene expression profiles of several Apc-mutant ESC lines encoding for different levels of Wnt signaling activation. We found that down-regulation of Tcf3, a member of the Tcf/Lef family and a key player in the control of self-renewal and pluripotency, represents a specific and primary response to Wnt activation in ESCs. Accordingly, rescuing Tcf3 expression partially restored the neural defects observed in Apc-mutant ESCs, suggesting that Tcf3 down-regulation is a necessary step towards Wnt-mediated suppression of neural differentiation. We found that Tcf3 down-regulation in the context of constitutively active Wnt signaling does not result from promoter DNA methylation but is likely to be caused by a plethora of mechanisms at both the RNA and protein level as shown by the observed decrease in activating histone marks (H3K4me3 and H3-acetylation) and the upregulation of miR-211, a novel Wnt-regulated microRNA that targets Tcf3 and attenuates early neural differentiation in mouse ESCs. Our data show for the first time that Wnt signaling down-regulates Tcf3 expression, possibly at both the transcriptional and post-transcriptional levels, and thus highlight a novel mechanism through which Wnt signaling inhibits neuro-ectodermal lineage differentiation in mouse embryonic stem cells.

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Section: Resultsmentioning

confidence: 99%

Wnt Signaling Regulates the Lineage Differentiation Potential of Mouse Embryonic Stem Cells through Tcf3 Down-Regulation

et al. 2013

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“…This was quite surprising, because the expression patterns of Tcf-4 are similar in mouse, zebrafish, and Xenopus, and one might have expected sequence similarities in the 5 0 -regions, which might be responsible for the restricted Tcf-4 expression in the developing brain. Interestingly, similar to the Tcf-3 promoter of X. tropicalis (Spieker et al, 2004), the XTcf-4 promoter of Xenopus laevis does not contain a TATA-box, but one potential Lef/ Tcf binding site (Fig. 1a).…”

Section: Resultsmentioning

confidence: 91%

“…Although the human Tcf-1 promoter and the X. tropicalis Tcf-3 promoter contain consensus Lef/Tcf binding sites, the physiological relevance of these sites has not been studied in detail so far. Strong activation of X. tropicalis Tcf-3 promoter during gastrulation depends on the presence of two wnt-responsive elements (Spieker et al, 2004), but it is not known yet whether these binding sites are activated by Lef/Tcf family members, nor if this region is endogenously occupied by these transcription factors. The hTcf-1 promoter has been shown to be responsive to b-catenin/Tcf-4 (Roose et al, 1999), but whether this regulation depends on one of the two consensus Lef/Tcf binding sites remains to be studied.…”

Section: Resultsmentioning

confidence: 99%

“…Thereby, the synexpressed Xwnt-2b is the main wnt-ligand necessary for XTcf-4 transcription. Although autoregulation of components of the wnt/b-catenin pathway is a wellstudied issue, and Lef-1, Tcf-1, Tcf-3, and Tcf-4 are described as wnt/b-catenin target genes (Hovanes et al, 2001;Kunz et al, 2004;Roose et al, 1999;Spieker et al, 2004), the molecular mechanism, how these transcription factors regulate their own expression, is poorly understood.…”

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confidence: 99%

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Autoregulation of XTcf‐4 depends on a Lef/Tcf site on the XTcf‐4 promoter

Koenig¹,

Lattanzio²,

Mansperger³

et al. 2008

Genesis

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The restricted expression of XTcf-4 in the anterior midbrain is regulated via an active wnt/beta-catenin pathway (Kunz et al.,2004, Dev Biol 273:390-401). The molecular mechanism of this autoregulatory loop, however, remained elusive. Here we show that the activity of a 1,775 bp promoter fragment containing a consensus Lef/Tcf binding site at position -1,437 to -1,428 is upregulated by activating transcription factors of the Lef/Tcf family. Furthermore, chromatin immunoprecipitation revealed that endogenous beta-catenin is bound to the Lef/Tcf site on the promoter. Thus, regulation of XTcf-4 by canonical wnt-signaling is directly controlled by binding to and activating a consensus Lef/Tcf binding site within its own promoter.

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“…Positive autoregulation has been described before for LEF1 in colon cancer [ 92 ], XTcf-4 (Tcf7l2) in Xenopus midbrain [ 93 ] and zebrafish Tcf3 (Tcf7l1) [ 95 ]. It is achieved through the direct binding of Tcf to its promoter [ 94 , 96 ], but, in vertebrates, this can be mediated by a different Tcf [ 97 ]. Interestingly, there was higher and broader Pdu - Tcf expression in the presence of Wnt/β-catenin inhibitors in the rest of the body, e.g.…”

Section: Discussionmentioning

confidence: 99%

Wnt/β-catenin signalling is necessary for gut differentiation in a marine annelid, Platynereis dumerilii

Žídek

Machoň

Kozmík

2018

EvoDevo

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BackgroundWnt/β-catenin (or canonical) signalling pathway activity is necessary and used independently several times for specification of vegetal fate and endoderm, gut differentiation, maintenance of epithelium in adult intestine and the development of gut-derived organs in various vertebrate and non-vertebrate organisms. However, its conservation in later stages of digestive tract development still remains questionable due to the lack of detailed data, mainly from Spiralia.ResultsHere we characterize the Pdu-Tcf gene, a Tcf/LEF orthologue and a component of Wnt/β-catenin pathway from Platynereis dumerilii, a spiralian, marine annelid worm. Pdu-Tcf undergoes extensive alternative splicing in the C-terminal region of the gene generating as many as eight mRNA isoforms some of which differ in the presence or absence of a C-clamp domain which suggests a distinct DNA binding activity of individual protein variants. Pdu-Tcf is broadly expressed throughout development which is indicative of many functions. One of the most prominent domains that exhibits rather strong Pdu-Tcf expression is in the putative precursors of endodermal gut cells which are detected after 72 h post-fertilization (hpf). At day 5 post-fertilization (dpf), Pdu-Tcf is expressed in the hindgut and pharynx (foregut), whereas at 7 dpf stage, it is strongly transcribed in the now-cellularized midgut for the first time. In order to gain insight into the role of Wnt/β-catenin signalling, we disrupted its activity using pharmacological inhibitors between day 5 and 7 of development. The inhibition of Wnt/β-catenin signalling led to the loss of midgut marker genes Subtilisin-1, Subtilisin-2, α-Amylase and Otx along with a drop in β-catenin protein levels, Axin expression in the gut and nearly the complete loss of proliferative activity throughout the body of larva. At the same time, a hindgut marker gene Legumain was expanded to the midgut compartment under the same conditions.ConclusionsOur findings suggest that high Wnt/β-catenin signalling in the midgut might be necessary for proper differentiation of the endoderm to an epithelium capable of secreting digestive enzymes. Together, our data provide evidence for the role of Wnt/β-catenin signalling in gut differentiation in Platynereis.

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Analysis of the Tcf‐3 promoter during early development of Xenopus

Cited by 5 publications

References 26 publications

Wnt Signaling Regulates the Lineage Differentiation Potential of Mouse Embryonic Stem Cells through Tcf3 Down-Regulation

Wnt Signaling Regulates the Lineage Differentiation Potential of Mouse Embryonic Stem Cells through Tcf3 Down-Regulation

Autoregulation of XTcf‐4 depends on a Lef/Tcf site on the XTcf‐4 promoter

Wnt/β-catenin signalling is necessary for gut differentiation in a marine annelid, Platynereis dumerilii

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