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Molecular and Cellular Biology, July 2000, p. 5087-5095, Vol. 20, No. 14
Program in Molecular Medicine, Department of
Cell Biology and Department of Biochemistry and Molecular
Biology1 and Department of Pharmacology
and Molecular Toxicology,3 University of
Massachusetts Medical School, Worcester, Massachusetts 01605, and
Genetics and Molecular Biology Branch, National Human
Genome Research Institute, National Institutes of Health, Bethesda,
Maryland 208922
Received 24 January 2000/Returned for modification 10 March
2000/Accepted 10 April 2000
Snail/Slug family proteins have been identified in diverse species
of both vertebrates and invertebrates. The proteins contain four to six
zinc fingers and function as DNA-binding transcriptional regulators.
Various members of the family have been demonstrated to regulate cell
movement, neural cell fate, left-right asymmetry, cell cycle, and
apoptosis. However, the molecular mechanisms of how these regulators
function and the target genes involved are largely unknown. In this
report, we demonstrate that human Slug (hSlug) is a repressor and
modulates both activator-dependent and basal transcription. The
repression depends on the C-terminal DNA-binding zinc fingers and on a
separable repression domain located in the N terminus. This domain may
recruit histone deacetylases to modify the chromatin and effect
repression. Protein localization study demonstrates that hSlug is
present in discrete foci in the nucleus. This subnuclear pattern does
not colocalize with the PML foci or the coiled bodies. Instead, the
hSlug foci overlap extensively with areas of the SC-35 staining, some
of which have been suggested to be sites of active splicing or
transcription. These results lead us to postulate that hSlug localizes
to target promoters, where activation occurs, to repress basal and
activator-mediated transcription.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Human Slug Is a Repressor That Localizes to
Sites of Active Transcription
*
Corresponding author. Mailing address: Program in
Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Worcester, MA 01605. Phone: (508) 856-5136. Fax: (508)
856-4289. E-mail: Tony.Ip{at}umassmed.edu.
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