PUBLICATION
Modulation of Tcf3 repressor complex composition regulates cdx4 expression in zebrafish
- Authors
- Ro, H., and Dawid, I.B.
- ID
- ZDB-PUB-110628-8
- Date
- 2011
- Source
- The EMBO journal 30(14): 2894-907 (Journal)
- Registered Authors
- Dawid, Igor B.
- Keywords
- caudal body domain, Cdx4, E4f1, Tcf3, Wnt signalling
- MeSH Terms
-
- Cells, Cultured
- Reverse Transcriptase Polymerase Chain Reaction
- Regulatory Sequences, Nucleic Acid
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Protein Binding
- Immunoprecipitation
- RNA, Messenger/genetics
- Histone Deacetylase 1/genetics
- Histone Deacetylase 1/metabolism
- Homeodomain Proteins/genetics*
- Homeodomain Proteins/metabolism
- Luciferases/metabolism
- Chromatin Immunoprecipitation
- Wnt Proteins/genetics
- Wnt Proteins/metabolism
- Animals
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- Ubiquitin-Protein Ligases/genetics
- Ubiquitin-Protein Ligases/metabolism
- Repressor Proteins/genetics
- Repressor Proteins/metabolism*
- Gene Expression Regulation, Developmental*
- Blotting, Western
- Promoter Regions, Genetic
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism
- Body Patterning
- PubMed
- 21666599 Full text @ EMBO J.
Citation
Ro, H., and Dawid, I.B. (2011) Modulation of Tcf3 repressor complex composition regulates cdx4 expression in zebrafish. The EMBO journal. 30(14):2894-907.
Abstract
The caudal homeobox (cdx) gene family is critical for specification of caudal body formation and erythropoiesis. In zebrafish, cdx4 expression is controlled by the Wnt pathway, but the molecular mechanism of this regulation is not fully understood. Here, we provide evidence that Tcf3 suppresses cdx4 expression through direct binding to multiple sites in the cdx4 gene regulatory region. Tcf3 requires corepressor molecules such as Groucho (Gro)/TLE and HDAC1 for activity. Using zebrafish embryos and cultured mammalian cells, we show that the transcription factor E4f1 derepresses cdx4 by dissociating corepressor proteins from Tcf3 without inhibiting its binding to cis-regulatory sites in the DNA. Further, the E3 ubiquitin ligase Lnx2b, acting as a scaffold protein irrespective of its enzymatic activity, counteracts the effects of E4f1. We propose that the modulation of Tcf3 repressor function by E4f1 assures precise and robust regulation of cdx4 expression in the caudal domain of the embryo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping