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Molecular and Cellular Biology, December 1999, p. 7961-7971, Vol. 19, No. 12
Division of Molecular Oncology, Washington
University School of Medicine, St. Louis, Missouri 63110
Received 5 February 1999/Returned for modification 5 March
1999/Accepted 30 August 1999
ZEB is a zinc finger-homeodomain protein that represses
transcription by binding to a subset of E-box sequences. ZEB inhibits muscle differentiation in mammalian systems, and its
Drosophila orthologue, zfh-1, inhibits somatic
and cardiac muscle differentiation during Drosophila
embryogenesis. ZEB also binds to the promoter of pivotal hematopoietic
genes (including those encoding interleukin-2, CD4, GATA-3, and
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Copyright © 1999, American Society for Microbiology. All rights reserved.
Independent Repressor Domains in ZEB Regulate
Muscle and T-Cell Differentiation
4-integrin), and mice in which ZEB has been genetically
targeted show thymic atrophy, severe defects in lymphocyte differentiation, and increased expression of the
4-integrin and CD4. Here, we demonstrate that ZEB
contains separate repressor domains which function in T lymphocytes and
muscle, respectively. The most C-terminal domain inhibits muscle
differentiation in mammalian cells by specifically blocking the
transcriptional activity of the myogenic factor MEF2C. The more
N-terminal domain blocks activity of hematopoietic transcription
factors such as c-myb, members of the ets
family, and TFE-III. Our results demonstrate that ZEB has evolved with
two independent repressor domains which target distinct sets of
transcription factors and function in different tissues.
*
Corresponding author. Mailing address: Division of
Molecular Oncology, Washington University School of Medicine, 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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