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Molecular and Cellular Biology, October 1999, p. 7255-7263, Vol. 19, No. 10
Division of Molecular
Oncology1 and Department of
Genetics,2 Washington University School of
Medicine, St. Louis, Missouri 63110
Received 13 April 1999/Returned for modification 25 May
1999/Accepted 15 June 1999
zfh-1 is a member of the zfh family of proteins, which all contain
zinc finger and homeodomains. The roles and mechanisms of action of
most family members are still unclear. However, we have shown
previously that another member of the family, the vertebrate ZEB
protein, is a transcriptional repressor that binds E box sequences and
inhibits myotube formation in cell culture assays. zfh-1 is downregulated in Drosophila embryos prior to myogenesis.
Embryos with zfh-1 loss-of-function mutation show alterations in the
number and position of embryonic somatic muscles, suggesting that zfh-1 could have a regulatory role in myogenesis. However, nothing is known
about the nature or mechanism of action of zfh-1. Here, we demonstrate
that zfh-1 is a transcription factor that binds E box sequences and
acts as an active transcriptional repressor. When zfh-1 expression was
maintained in the embryo beyond its normal temporal pattern of
downregulation, the differentiation of somatic but not visceral muscle
was blocked. One potential target of zfh-1 in somatic myogenesis could
be the myogenic factor mef2. mef2 is known to be regulated by the
transcription factor twist, and we show here that zfh-1 binds to sites
in the mef2 upstream regulatory region and inhibits twist
transcriptional activation. Even though there is little sequence
similarity in the repressor domains of ZEB and zfh-1, we present
evidence that zfh-1 is the functional homologue of ZEB and that the
role of these proteins in myogenesis is conserved from
Drosophila to mammals.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
zfh-1, the Drosophila Homologue of ZEB,
Is a Transcriptional Repressor That Regulates Somatic
Myogenesis
*
Corresponding author. Mailing address: Washington
University School of Medicine, Division of Molecular Oncology, Campus
Box 8069, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314)
362-8989. Fax: (314) 747-2797. E-mail:
ddean{at}im.wustl.edu.
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