Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators

Yaklichkin, Sergey; Vekker, Alexander; Stayrook, Steven E.; Lewis, Mitchell; Kessler, Daniel S.

doi:10.1186/1471-2164-8-201

Cited by 40 publications

(55 citation statements)

References 39 publications

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“…By contrast, we identified an N-terminal eh1 motif in FoxG1 as the main binding site for TLE2. Although the co-IP assay does not allow us to conclude with certainty that the interaction between FoxG1 and Groucho/TLE is direct, the eh1 motif shows the strongest conservation with known TLE binding sites (Yaklichkin et al, 2007a;Yaklichkin et al, 2007b).…”

Section: The N-terminal Eh1 Motif Is Important For Physical Associatimentioning

confidence: 87%

“…The binding of TLEs to their target transcription factors is, in most cases, mediated via their WDR domain. This domain recognises two conserved motifs in the proteins that TLEs interact with: a WRPW motif and an engrailed homology 1 (eh1) domain, FXIXXIL (reviewed by Buscarlet and Stifani, 2007;Gasperowicz and Otto, 2005), which is present in eight classes of the homeodomain protein superfamily and in more than 50% of all members of the Fox family (Buscarlet and Stifani, 2007;Gasperowicz and Otto, 2005;Yaklichkin et al, 2007b). An interaction between human TLE1 and murine or chicken Foxg1 has been mapped to a C-terminal domain of Foxg1 (Sonderegger and Vogt, 2003;Yao et al, 2001), comprising amino acids 276-336 of mouse Foxg1 (which corresponds to amino acids 229-292 in Xenopus FoxG1).…”

Section: Tle2 and Foxg1 Physically Interact Via An N-terminal Eh1 Dommentioning

confidence: 99%

“…A computational analysis of eh1 motifs within the Fox family of transcription factors revealed that in addition to the fully conserved eh1 motif at the N-terminus (F18SINSLV), there is a 'remnant' eh1 motif in the C-terminal region of FoxG1 that lacks the highly conserved phenylalanine [L309SVDRLV (Yaklichkin et al, 2007b)]. Mutation of the four hydrophobic amino acid residues of the remnant C-terminal eh1 motif to alanines (FoxG1-C4A-HA) did not affect TLE binding (Fig.…”

Section: Injection Of X Tropicalis Foxg1 Mrna Gave Rise To Similar Pmentioning

confidence: 99%

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FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation

et al. 2010

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SUMMARYFoxG1 is a conserved transcriptional repressor that plays a key role in the specification, proliferation and differentiation of the telencephalon, and is expressed from the earliest stages of telencephalic development through to the adult. How the interaction with co-factors might influence the multiplicity and diversity of FoxG1 function is not known. Here, we show that interaction of FoxG1 with TLE2, a Xenopus tropicalis co-repressor of the Groucho/TLE family, is crucial for regulating the early activity of FoxG1. We show that TLE2 is co-expressed with FoxG1 in the ventral telencephalon from the early neural plate stage and functionally cooperates with FoxG1 in an ectopic neurogenesis assay. FoxG1 has two potential TLE binding sites: an N-terminal eh1 motif and a C-terminal YWPMSPF motif. Although direct binding seems to be mediated by the N-terminal motif, both motifs appear important for functional synergism. In the neurogenesis assay, mutation of either motif abolishes functional cooperation of TLE2 with FoxG1, whereas in the forebrain deletion of both motifs renders FoxG1 unable to induce the ventral telencephalic marker Nkx2.1. Knocking down either FoxG1 or TLE2 disrupts the development of the ventral telencephalon, supporting the idea that endogenous TLE2 and FoxG1 work together to specify the ventral telencephalon.

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Section: The N-terminal Eh1 Motif Is Important For Physical Associatimentioning

confidence: 87%

Section: Tle2 and Foxg1 Physically Interact Via An N-terminal Eh1 Dommentioning

confidence: 99%

Section: Injection Of X Tropicalis Foxg1 Mrna Gave Rise To Similar Pmentioning

confidence: 99%

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FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation

et al. 2010

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“…These cells give rise to the anteriormost derivatives of the CNS, including the anterior brain and stomodeum. (Yaklichkin et al, 2007). Interestingly, this conserved repressor motif is absent from the Ciona FoxC ortholog.…”

Section: Research Articlementioning

confidence: 99%

FGF signaling establishes the anterior border of the Ciona neural tube

2012

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SUMMARYThe Ciona tadpole is constructed from simple, well-defined cell lineages governed by provisional gene networks that have been defined via extensive gene disruption assays. Here, we examine the patterning of the anterior neural plate, which produces placodal derivatives such as the adhesive palps and stomodeum, as well as the sensory vesicle (simple brain) of the Ciona tadpole. Evidence is presented that the doublesex-related gene DMRT is expressed throughout the anterior neural plate of neurulating embryos. It leads to the activation of FoxC and ZicL in the palp placode and anterior neural tube, respectively. This differential expression depends on FGF signaling, which inhibits FoxC expression in the anterior neural tube. Inhibition of FGF signaling leads to expanded expression of FoxC, the loss of ZicL, and truncation of the anterior neural tube.

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“…DNA-binding motifs are similar for many forkhead transcription factors and functional diversity is determined by flanking domains that interact with distinct co-factors (Gajiwala and Burley, 2000;Overdier et al, 1994;Pierrou et al, 1994). In vivo transcriptional targets and mechanisms of regulation have not yet been determined for the majority of forkhead transcription factors, although many family members are known to associate with the Groucho co-repressor (Yaklichkin et al, 2007a;Yaklichkin et al, 2007b). In this article, we focus on understanding the mechanism of action of FOXD1, which is required for kidney development (Hatini et al, 1996;Levinson et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney

et al. 2014

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Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. Foxd1 is required during kidney development and its inactivation results in failure of nephron progenitor cell differentiation. Foxd1 is expressed in interstitial cells adjacent to nephron progenitor cells, suggesting an essential role for the progenitor cell niche in nephrogenesis. To better understand how cortical interstitial cells in general, and FOXD1 in particular, influence the progenitor cell niche, we examined the differentiation states of two progenitor cell subtypes in Foxd1 −/− tissue. We found that although nephron progenitor cells are retained in a primitive CITED1-expressing compartment, cortical interstitial cells prematurely differentiate. To identify pathways regulated by FOXD1, we screened for target genes by comparison of Foxd1 null and wild-type tissues. We found that the gene encoding the small leucine-rich proteoglycan decorin (DCN) is repressed by FOXD1 in cortical interstitial cells, and we show that compound genetic inactivation of Dcn partially rescues the failure of progenitor cell differentiation in the Foxd1 null. We demonstrate that DCN antagonizes BMP/SMAD signaling, which is required for the transition of CITED1-expressing nephron progenitor cells to a state that is primed for WNT-induced epithelial differentiation. On the basis of these studies, we propose a mechanism for progenitor cell retention in the Foxd1 null in which misexpressed DCN produced by prematurely differentiated interstitial cells accumulates in the extracellular matrix, inhibiting BMP7-mediated transition of nephron progenitor cells to a compartment in which they can respond to epithelial induction signals.

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Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators

Cited by 40 publications

References 39 publications

FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation

FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation

FGF signaling establishes the anterior border of the Ciona neural tube

FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney

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