Document Detail

Modulation of Tcf3 repressor complex composition regulates cdx4 expression in zebrafish.
MedLine Citation:
PMID:  21666599     Owner:  NLM     Status:  MEDLINE    
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.
Hyunju Ro; Igor B Dawid
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2011-06-10
Journal Detail:
Title:  The EMBO journal     Volume:  30     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-20     Completed Date:  2011-09-29     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2894-907     Citation Subset:  IM    
Laboratory of Molecular Genetics, Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
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MeSH Terms
Blotting, Western
Body Patterning
Cells, Cultured
Chromatin Immunoprecipitation
Embryo, Nonmammalian / cytology,  metabolism
Gene Expression Regulation, Developmental*
Histone Deacetylase 1 / genetics,  metabolism
Homeodomain Proteins / genetics*,  metabolism
Luciferases / metabolism
Promoter Regions, Genetic
Protein Binding
RNA, Messenger / genetics
Regulatory Sequences, Nucleic Acid
Repressor Proteins / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Ubiquitin-Protein Ligases / genetics,  metabolism
Wnt Proteins / genetics,  metabolism
Zebrafish / embryology*,  genetics,  metabolism
Zebrafish Proteins / genetics,  metabolism*
Reg. No./Substance:
0/Homeodomain Proteins; 0/RNA, Messenger; 0/Repressor Proteins; 0/Tcf3 protein, zebrafish; 0/Wnt Proteins; 0/Zebrafish Proteins; 0/cdx4 protein, zebrafish; 0/gro3 protein, zebrafish; EC 1.13.12.-/Luciferases; EC protein, zebrafish; EC Deacetylase 1; EC Ligases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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