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

[holt-oram syndrome]

TBX 5 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 TBX 5 and MEF 2 C leading to a synergistic activation of the alpha-cardiac myosin heavy chain (MYH 6 ). Mutants of TBX 5 , TBX 5 G 8 0 R , and TBX 5 R 279 X that produce severe cardiac phenotypes impair the synergy . Using fluorescence resonance energy transfer , we demonstrate the interaction of TBX 5 and MEF 2 C in living cells . We also show that they physically associate through their DNA-binding domains to form a complex on the MYH 6 promoter . Morpholino-mediated knockdowns of Tbx 5 and Mef 2 c in zebrafish suggest that the genetic interaction of these proteins is not only required for MYH 6 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 .