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Nuclear matrix binding regulates SATB1-mediated transcriptional repression
Jin Seo1, Mary M Lozano, Jaquelin P Dudley
1Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA.
The Journal of Biological Chemistry
|April 27, 2005
Summary
Special AT-rich binding protein 1 (SATB1) is crucial for gene repression. Its nuclear matrix targeting sequence (NMTS) and DNA binding are essential for optimal repression of the MMTV promoter.
Area of Science:
- Molecular Biology
- Epigenetics
- Gene Regulation
Background:
- Special AT-rich binding protein 1 (SATB1) binds nuclear matrix attachment regions (MARs).
- SATB1 represses thymus-expressed genes, including MMTV, a glucocorticoid-responsive retrovirus.
Purpose of the Study:
- To investigate the role of the nuclear matrix in SATB1-mediated gene repression.
- To identify the SATB1 domains critical for nuclear matrix localization and transcriptional repression.
Main Methods:
- Used SATB1 deletion constructs to assess protein localization and function.
- Employed retroviral vectors to study SATB1 domain effects on MMTV promoter activity.
- Performed transient transfection assays with NMTS-green fluorescent protein or LexA fusions.
Main Results:
- Identified a nuclear matrix targeting sequence (NMTS) within SATB1 (amino acids 224-278).
- SATB1 overexpression repressed MMTV transcription, dependent on both NMTS and MAR-binding domains.
- Deletion of NMTS or MAR-binding domain alleviated repression.
Conclusions:
- Nuclear matrix association and DNA binding are both required for SATB1's optimal repression of the MMTV promoter.
- SATB1 may utilize nuclear matrix association for insulation from regulatory elements.