A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome.

[holt-oram syndrome]

The T -box transcription factor TBX 5 plays essential roles in cardiac and limb development . Various mutations in the TBX 5 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 TBX 5 coactivator . TAZ directly associates with TBX 5 and markedly stimulates TBX 5 -dependent promoters by interacting with the histone acetyltransferases p 300 and PCAF . YAP , a TAZ -related protein with conserved functional domains , also stimulates TBX 5 -dependent transcription , possibly by forming a heterodimer with TAZ . TBX 5 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 TBX 5 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 TBX 5 -dependent transcription and suggest the involvement of these coactivators in cardiac and limb development .