ZFIN ID: ZDB-PUB-080326-2
Activator-to-repressor conversion of T-box transcription factors by the Ripply family of Groucho/TLE-associated mediators
Kawamura, A., Koshida, S., and Takada, S.
Date: 2008
Source: Molecular and cellular biology 28(10): 3236-3244 (Journal)
Registered Authors: Kawamura, Akinori, Koshida, Sumito, Takada, Shinji
Keywords: none
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*
PubMed: 18332117 Full text @ Mol. Cell. Biol.
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ABSTRACT
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.
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