Activator-to-repressor conversion of T-box transcription factors by the Ripply family of Groucho/TLE-associated mediators

Mol Cell Biol. 2008 May;28(10):3236-44. doi: 10.1128/MCB.01754-07. Epub 2008 Mar 10.


The T-box family of transcription factors, defined by a conserved DNA binding domain called the T-box, regulate various aspects of embryogenesis by activating and/or repressing downstream genes. In spite of the biological significance of the T-box proteins, how they regulate transcription remains to be elucidated. Here we show that the Groucho/TLE-associated protein Ripply converts T-box proteins from activators to repressors. In cultured cells, zebrafish Ripply1, an essential component in somite segmentation, and its structural relatives, Ripply2 and -3, suppress the transcriptional activation mediated by the T-box protein Tbx24, which is coexpressed with ripply1 during segmentation. Ripply1 associates with Tbx24 and converts it to a repressor. Ripply1 also antagonizes the transcriptional activation of another T-box protein, No tail (Ntl), the zebrafish ortholog of Brachyury. Furthermore, injection of a high dosage of ripply1 mRNA into zebrafish eggs causes defective development of the posterior trunk, similar to the phenotype observed in homozygous mutants of ntl. A mutant form of Ripply1 defective in association with Tbx24 also lacks activity in zebrafish embryos. These results indicate that the intrinsic transcriptional property of T-box proteins is controlled by Ripply family proteins, which act as specific adaptors that recruit the global corepressor Groucho/TLE to T-box proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Binding Sites
  • Cell Line
  • Humans
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oligodeoxyribonucleotides, Antisense / genetics
  • Plasmids / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transcriptional Activation
  • Transfection
  • Up-Regulation
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Basic Helix-Loop-Helix Transcription Factors
  • Nuclear Proteins
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Messenger
  • Recombinant Proteins
  • Repressor Proteins
  • T-Box Domain Proteins
  • Zebrafish Proteins
  • mespba protein, zebrafish
  • ripply1 protein, zebrafish
  • tbx6 protein, zebrafish