Transcription repression by Xenopus ET and its human ortholog TBX3, a geneinvolved in ulnar-mammary syndrome

Tbox (Tbx) genes are a family of developmental regulators with more than 20 members recently identified in invertebrates and vertebrates, Mutations in Tbx genes have been found to cause several human diseases. Our understandi ng of functional mechanisms of Tbx products has come mainly from the protot ypical T/Brachyury, which is a transcription activator. We previously disco vered ET, a Tbx gene expressed in Xenopus embryos. We report here that ET i s an ortholog of the human Tbx3 and that ET is a repressor of basal and act ivated transcription. Functional dissection of the ET protein reveals a nov el transcription-repression domain highly conserved among FT, human TBX3, a nd TBX2. These results reveal a new transcription repressor domain, show th e existence of a subfamily of transcription repressors in the Tbx superfami ly, and provide a basis for understanding etiology of diseases caused by Tb x3 mutations.