PUBLICATION
Activator-to-repressor conversion of T-box transcription factors by the Ripply family of Groucho/TLE-associated mediators
- Authors
- Kawamura, A., Koshida, S., and Takada, S.
- ID
- ZDB-PUB-080326-2
- 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.
Citation
Kawamura, A., Koshida, S., and Takada, S. (2008) Activator-to-repressor conversion of T-box transcription factors by the Ripply family of Groucho/TLE-associated mediators. Molecular and cellular biology. 28(10):3236-3244.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping