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Looking Inside T-box

T-box (Tbx) genes encode a family of transcription factors that regulate a variety of developmental processes. Tbx18 and Tbx15 encode a closely related pair of T-box proteins that, together with Tbx22, form a subgroup of the Tbx1 subfamily in vertebrates. Functional analyses in mice have shown that Tbx15 is needed for skin and skeletal development and that Tbx18 is required for the formation of the vertebral column, the ureter, and the posterior pole of the heart. Despite this knowledge of the embryological roles of the proteins, it is currently unclear how Tbx18 and Tbx15 exert their function at the molecular level.

Overexpression of Tbx18 coincides with down-regulation of Dll1 and Hey1.

In this Paper of the Week, Henner F. Farin and colleagues characterize the subcellular localization, DNA binding specificities, protein interactions and transcriptional properties, and structural prerequisites of the two proteins. They show that both proteins homo- and heterodimerize, bind to various combinations of T half-sites, and repress transcription by interacting with proteins in the Groucho family of corepressors. The authors also provide evidence that competition with activating T-box proteins constitutes a possible mode of regulation of the promoters for Nppa and Dll1 in vitro and in vivo.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 25748-25759

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