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J. Biol. Chem., Vol. 276, Issue 16, 13121-13126, April 20, 2001
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From the Department of Biochemistry, University of Kentucky,
Lexington, Kentucky 40563-0298
The transcription factor neuron-restrictive
silencer factor/repressor element-1 (RE-1) silencing
transcription factor (NRSF/REST) contains nine zinc finger domains and
binds to the DNA element, neuron-restrictive silencer element/repressor
element-1. REST4, a C-terminally truncated form of NRSF/REST, contains
the five N-terminal zinc fingers and binds weakly to DNA yet is
transported into the nucleus. To study the contribution of zinc fingers
6-8 to DNA binding, each was mutated. A mutation in zinc finger 6 or 8 had little effect; however, mutation of zinc finger 7 diminished DNA
binding. Mutations in any two of these zinc fingers eliminated DNA
binding. The contribution of zinc fingers 2-5 to nuclear targeting was
studied. Deletion of zinc finger 5 prevented nuclear targeting. Mutations in zinc finger 2, 4, or 5 did not abolish nuclear targeting. However, a zinc finger 3 mutation together with a zinc finger 2 mutation localized to the nuclear envelope. A zinc finger 3 mutation
alone or in combination with a zinc finger 4 or 5 mutation produced a
punctate nuclear distribution. These results suggest the presence of
signals for nuclear targeting, for nuclear entry, and for release from
the translocation machinery within zinc fingers 2-5 of REST4.
Role of Zinc Finger Domains of the Transcription Factor
Neuron-restrictive Silencer Factor/Repressor Element-1 Silencing
Transcription Factor in DNA Binding and Nuclear Localization*
*
This work was supported in part by NIA, National Institutes
of Health, Grant AG05893.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biochemistry,
University of Kentucky, Chandler Medical Center, 800 Rose St.,
Lexington, KY 40536-0298. Tel.: 859-323-5549; Fax: 859-323-1727; E-mail: lhersh@pop.uky.edu.
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