Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila

Bhambhani, Chandan; Ravindranath, Aditi J.; Mentink, Remco A.; Chang, Mikyung V.; Betist, Marco C.; Yang, Yaxuan; Koushika, Sandhya P.; Korswagen, Hendrik C.; Cadigan, Ken M.

doi:10.1371/journal.pgen.1004133

Cited by 33 publications

(48 citation statements)

References 108 publications

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“…Consistent with this observation, the end promoters contain binding sites for the maternal factors SKN-1, POP-1 and PAL-1 (Fig. 2, Table S1) (Bhambhani et al, 2014; Blackwell et al, 1994; Korswagen et al, 2000; Lei et al, 2009). Of these, SKN-1 accounts for the majority of input into end activation, as loss of skn-1 activity results in a failure of gut specification in 65–80% of embryos (Bowerman et al, 1992; Huang et al, 2007; Maduro et al, 2005b).…”

Section: Resultssupporting

confidence: 73%

“…While POP-1-dependent repression of the end s occurs via POP-1 sites (alone), POP-1-dependent activation requires the nearby presence of conserved ‘Helper’ sites through which the POP-1/SYS-1 complex likely binds (Bhambhani et al, 2014; Robertson et al, 2014; Shetty et al, 2005). The end-1 promoter contains a nearby POP-1+Helper site (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The end-1 promoter contains a nearby POP-1+Helper site (Fig. 2 and Table S1), and these sites mediate a positive contribution of POP-1 to end-1 activation (Bhambhani et al, 2014; Shetty et al, 2005). In contrast, the end-3 promoter has POP-1 sites and putative Helper sites, though the best consensus Helper sites are not near the POP-1 sites (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In the MS nucleus, the ratio of POP-1 to SYS-1 is high, resulting in repression of endoderm fate (Huang et al, 2007; Maduro et al, 2007; Shetty et al, 2005). A recent report identified a requirement for conserved cis- regulatory sites, proximal to POP-1 sites, to which POP-1/SYS-1 bind during Wnt-dependent target gene activation (Bhambhani et al, 2014). These Helper sites appear to be absent in end-3 , suggesting that the activation component of POP-1/SYS-1 in E specification occurs primarily through end-1 (Bhambhani et al, 2014; Robertson et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…A recent report identified a requirement for conserved cis- regulatory sites, proximal to POP-1 sites, to which POP-1/SYS-1 bind during Wnt-dependent target gene activation (Bhambhani et al, 2014). These Helper sites appear to be absent in end-3 , suggesting that the activation component of POP-1/SYS-1 in E specification occurs primarily through end-1 (Bhambhani et al, 2014; Robertson et al, 2014). While Wnt-activated POP-1 contributes to endoderm specification, it is not essential, as >95% of pop-1 -depleted embryos still make gut (Lin et al, 1995; Maduro et al, 2007; Maduro et al, 2005b).…”

Section: Introductionmentioning

confidence: 99%

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MED GATA factors promote robust development of the C. elegans endoderm

Maduro

Broitman-Maduro

Choi

et al. 2015

Developmental Biology

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The MED-1,2 GATA factors contribute to specification of E, the progenitor of the C. elegans endoderm, through the genes end-1 and end-3, and in parallel with the maternal factors SKN-1, POP-1 and PAL-1. END-1,3 activate elt-2 and elt-7 to initiate a program of intestinal development, which is maintained by positive autoregulation. Here, we advance the understanding of MED-1,2 in E specification. We find that expression of end-1 and end-3 is greatly reduced in med-1,2(−) embryos. We generated strains in which MED sites have been mutated in end-1 and end-3. Without MED input, gut specification relies primarily on POP-1 and PAL-1. 25% of embryos fail to make intestine, while those that do display abnormal numbers of gut cells due to a delayed and stochastic acquisition of intestine fate. Surviving adults exhibit phenotypes consistent with a primary defect in the intestine. Our results establish that MED-1,2 provide robustness to endoderm specification through end-1 and end-3, and reveal that gut differentiation may be more directly linked to specification than previously appreciated. The results argue against an “all-or-none” description of cell specification, and suggest that activation of tissue-specific master regulators, even when expression of these is maintained by positive autoregulation, does not guarantee proper function of differentiated cells.

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Section: Resultssupporting

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

MED GATA factors promote robust development of the C. elegans endoderm

Maduro

Broitman-Maduro

Choi

et al. 2015

Developmental Biology

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The Wnt Transcriptional Switch: TLE Removal or Inactivation?

et al. 2017

Self Cite

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Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a "transcriptional switch," repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway.

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Wnt Signaling Polarizes C. elegans Asymmetric Cell Divisions During Development

Lam

Phillips

2017

Results and Problems in Cell Differentiation

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Asymmetric cell division is a common mode of cell differentiation during the invariant lineage of the nematode, C. elegans. Beginning at the four-cell stage, and continuing throughout embryogenesis and larval development, mother cells are polarized by Wnt ligands, causing an asymmetric inheritance of key members of a Wnt/β-catenin signal transduction pathway termed the Wnt/β-catenin asymmetry pathway. The resulting daughter cells are distinct at birth with one daughter cell activating Wnt target gene expression via β-catenin activation of TCF, while the other daughter displays transcriptional repression of these target genes. Here, we seek to review the body of evidence underlying a unified model for Wnt-driven asymmetric cell division in C. elegans, identify global themes that occur during asymmetric cell division as well as highlight tissue-specific variations. We also discuss outstanding questions that remain unanswered regarding this intriguing mode of asymmetric cell division.

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Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila

Cited by 33 publications

References 108 publications

MED GATA factors promote robust development of the C. elegans endoderm

MED GATA factors promote robust development of the C. elegans endoderm

The Wnt Transcriptional Switch: TLE Removal or Inactivation?

Wnt Signaling Polarizes C. elegans Asymmetric Cell Divisions During Development

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