The T-box transcription factor TBX5 plays essential roles in cardiac and limb 
development. Various mutations in the TBX5 gene have been identified in patients 
with Holt-Oram syndrome, which is characterized by congenital defects in the 
heart and upper extremities. In this study, we identified a WW-domain-containing 
transcriptional regulator TAZ as a potent TBX5 coactivator. TAZ directly 
associates with TBX5 and markedly stimulates TBX5-dependent promoters by 
interacting with the histone acetyltransferases p300 and PCAF. YAP, a 
TAZ-related protein with conserved functional domains, also stimulates 
TBX5-dependent transcription, possibly by forming a heterodimer with TAZ. TBX5 
lacks a PY motif, which mediates the association of other proteins with TAZ, and 
interacts with TAZ through multiple domains including its carboxyl-terminal 
structure. Truncation mutants of TBX5 identified in patients with Holt-Oram 
syndrome were markedly impaired in their ability to associate with and be 
stimulated by TAZ. These findings reveal key roles for TAZ and YAP in the 
control of TBX5-dependent transcription and suggest the involvement of these 
coactivators in cardiac and limb development.