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PMID: 19204083 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Physical interaction between TBX5 and MEF2C is required for early heart development.

Molecular and cellular biology ·Vol. 29 ·No. 8 ·2009-04-00 ·Pages 2205-18

Ghosh TK, Song FF, Packham EA, Buxton S, Robinson TE, Ronksley J, Self T, Bonser AJ, Brook JD

Abstract

TBX5 is a transcription factor which plays important roles in the development of the heart and upper limbs. Mutations in this gene produce the inherited disorder Holt-Oram syndrome. Here, we report a physical interaction between TBX5 and MEF2C leading to a synergistic activation of the alpha-cardiac myosin heavy chain (MYH6). Mutants of TBX5, TBX5G80R, and TBX5R279X that produce severe cardiac phenotypes impair the synergy. Using fluorescence resonance energy transfer, we demonstrate the interaction of TBX5 and MEF2C in living cells. We also show that they physically associate through their DNA-binding domains to form a complex on the MYH6 promoter. Morpholino-mediated knockdowns of Tbx5 and Mef2c in zebrafish suggest that the genetic interaction of these proteins is not only required for MYH6 expression but also essential for the early stages of heart development and survival. This is the first report of a functional interaction between a T-box protein and a MADS box factor that may be crucial in cardiomyocyte differentiation.

MeSH Terms
Animals Cardiac Myosins/genetics Cell Line Embryo, Nonmammalian Heart/growth & development Humans Mutation, Missense Myogenic Regulatory Factors/metabolism,physiology Myosin Heavy Chains/genetics Promoter Regions, Genetic Rats T-Box Domain Proteins/genetics,metabolism,physiology Transfection Zebrafish
Chemicals
MYH6 protein, human Myogenic Regulatory Factors T-Box Domain Proteins T-box transcription factor 5 Cardiac Myosins Myosin Heavy Chains
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ghosh Tushar K
Institute of Genetics, School of Biology, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom.
Song Fei Fei
Packham Elizabeth A
Buxton Sarah
Robinson Thelma E
Ronksley Jonathan
Self Tim
Bonser Andrew J
Brook J David
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01923-08
Published
2009-04-00
Epub
2009-00-09
Pages
2205-18
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2663302
Subset
IM
Grants
British Heart Foundation · RG/07/010/23676 · United Kingdom
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1128/MCB.01923-08 PMC Full Text View journal details
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