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

被引:58
作者
Shimojo, M [1 ]
Lee, JH [1 ]
Hersh, LB [1 ]
机构
[1] Univ Kentucky, Albert B Chandler Med Ctr, Dept Biochem, Lexington, KY 40536 USA
关键词
D O I
10.1074/jbc.M011193200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 REST 4.
引用
收藏
页码:13121 / 13126
页数:6
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