Functional analyses of vertebrate TCF proteins in C. elegans embryos

Scott M. Robertson, Miao Chia Lo, Ranaan Odom, Xiao Dong Yang, Jessica Medina, Shuyi Huang, Rueyling Lin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

In the canonical Wnt pathway, signaling results in the stabilization and increased levels of β-catenin in responding cells. β-catenin then enters the nucleus, functioning as a coactivator for the Wnt effector, TCF/LEF protein. In the absence of Wnt signaling, TCF is complexed with corepressors, together repressing Wnt target genes. In C. elegans, Wnt signaling specifies the E blastomere to become the endoderm precursor. Activation of endoderm genes in E requires not only an increase in β-catenin level, but a concomitant decrease in the nuclear level of POP-1, the sole C. elegans TCF. A decrease in nuclear POP-1 levels requires Wnt-induced phosphorylation of POP-1 and 14-3-3 protein-mediated nuclear export. Nuclear POP-1 levels remain high in the sister cell of E, MS, where POP-1 represses the expression of endoderm genes. Here we express three vertebrate TCF proteins (human TCF4, mouse LEF1 and Xenopus TCF3) in C. elegans embryos and compare their localization, repression and activation functions to POP-1. All three TCFs are localized to the nucleus in C. elegans embryos, but none undergoes Wnt-induced nuclear export. Although unable to undergo Wnt-induced nuclear export, human TCF4, but not mouse LEF1 or Xenopus TCF3, can repress endoderm genes in MS, in a manner very similar to POP-1. This repressive activity requires that human TCF4 recognizes specific promoter sequences upstream of endoderm genes and interacts with C. elegans corepressors. Domain swapping identified two regions of POP-1 that are sufficient to confer nuclear asymmetry to human TCF4 when swapped with its corresponding domains. Despite undergoing Wnt-induced nuclear export, the human TCF4/POP-1 chimeric protein continues to function as a repressor for endoderm genes in E, a result we attribute to the inability of hTCF4 to bind to C. elegans β-catenin. Our results reveal a higher degree of species specificity among TCF proteins for coactivator interactions than for corepressor interactions, and uncover a basic difference between how POP-1 and human TCF4 steady state nuclear levels are regulated.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalDevelopmental Biology
Volume355
Issue number1
DOIs
StatePublished - Jul 1 2011

Fingerprint

Caenorhabditis elegans Proteins
Endoderm
Vertebrates
Catenins
Cell Nucleus Active Transport
Embryonic Structures
Co-Repressor Proteins
Xenopus
Genes
14-3-3 Proteins
Species Specificity
Blastomeres
Wnt Signaling Pathway
Proteins
Human Activities
Transcriptional Activation
Phosphorylation
Gene Expression

Keywords

  • A-P asymmetry
  • C. elegans
  • POP-1
  • Vertebrate TCF
  • Wnt signaling

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Functional analyses of vertebrate TCF proteins in C. elegans embryos. / Robertson, Scott M.; Lo, Miao Chia; Odom, Ranaan; Yang, Xiao Dong; Medina, Jessica; Huang, Shuyi; Lin, Rueyling.

In: Developmental Biology, Vol. 355, No. 1, 01.07.2011, p. 115-123.

Research output: Contribution to journalArticle

Robertson, SM, Lo, MC, Odom, R, Yang, XD, Medina, J, Huang, S & Lin, R 2011, 'Functional analyses of vertebrate TCF proteins in C. elegans embryos', Developmental Biology, vol. 355, no. 1, pp. 115-123. https://doi.org/10.1016/j.ydbio.2011.04.012
Robertson, Scott M. ; Lo, Miao Chia ; Odom, Ranaan ; Yang, Xiao Dong ; Medina, Jessica ; Huang, Shuyi ; Lin, Rueyling. / Functional analyses of vertebrate TCF proteins in C. elegans embryos. In: Developmental Biology. 2011 ; Vol. 355, No. 1. pp. 115-123.
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