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
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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.
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SRRM4 promotes splicing of the REST4 isoform, which has reduced transcriptional repression activity.
“SRRM4 promotes splicing of the REST4 isoform, which lacks four of the nine zinc fingers found in the full-length protein31 and has reduced transcriptional repression activity32–34.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [33]
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The neurogenetics of alternative splicing
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- Authors
- Shimojo, M., Lee, J.-H., & Hersh, L. B.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Hersh, Louis B.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 276
- Issue
- 16
- Pages
- 13121-13126
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1977779000
- Cited by
- 65
- References
- 24
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 5 · 2014: 1 · 2013: 2
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-05893)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- rest, NRSF, zinc finger, DNA binding, nuclear localization, nuclear targeting, transcription factors, zinc finger mutations, nuclear envelope, nuclear translocation, neuron-restrictive silencer element
- MeSH terms
- RE1-Silencing Transcription Factor, Base Sequence, beta-Galactosidase, Binding Sites, Cell Line, Cell Nucleus, DNA, Humans, Luminescent Proteins, Molecular Sequence Data, Recombinant Fusion Proteins, Recombinant Proteins, Repressor Proteins, Templates, Genetic, Transcription Factors, Transfection, Mutagenesis, Zinc Fingers, Sequence Deletion, DNA Primers, Green Fluorescent Proteins
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