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Originally published In Press as doi:10.1074/jbc.M707085200 on September 24, 2007

J. Biol. Chem., Vol. 282, Issue 48, 34623-34633, November 30, 2007
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Mechanism of Transcriptional Activation by the Proto-oncogene Twist1*{diamondsuit}

Kristian Bruun Laursen{ddagger}, Esther Mielke{ddagger}, Philip Iannaccone§, and Ernst-Martin Füchtbauer{ddagger}1

From the {ddagger}Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus C, Denmark and the §Developmental Biology Program, Children's Memorial Research Center, Northwestern University, Chicago, Illinois 60614

Mammalian Twist1, a master regulator in development and a key factor in tumorigenesis, is known to repress transcription by several mechanisms and is therefore considered to mediate its function mainly through inhibition. A role of Twist1 as transactivator has also been reported but, so far, without providing a mechanism for such an activity. Here we show that heterodimeric complexes of Twist1 and E12 mediate E-box-dependent transcriptional activation. We identify a novel Twist1 transactivation domain that coactivates together with the less potent E12 transactivation domain. We found three specific residues in the highly conserved WR domain to be essential for the transactivating function of murine Twist1 and suggest an {alpha}-helical structure of the transactivation domain.


Received for publication, August 23, 2007 , and in revised form, September 24, 2007.

* This work was supported by grants from the Deutsche Forschungsgemeinschaft (Grant Fu329/2-1), the Danish Cancer Society (Grant DP 00 086), the Arne Hansen Foundation, the Faculty of Science, University of Aarhus, George M. Eisenberg Foundation for Charities, and the Illinois Regenerative Medicine Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{diamondsuit} This article was selected as a Paper of the Week.

1 To whom correspondence should be addressed: Institute of Molecular Biology, C.F. Møllers Allé 130, 3., University of Aarhus, DK-8000 Aarhus C, Denmark. Tel.: 45-89-422-738; E-mail: emf{at}mb.au.dk.


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