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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
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Chromatin-remodeling for transcription.
Yahli Lorch1, Roger D Kornberg1
1Department of Structural Biology,Stanford University School of Medicine,Stanford,CA 94305,USA.
Quarterly Reviews of Biophysics
|December 14, 2017
Summary
Chromatin remodeling complexes like RSC alter nucleosome structure to enable gene transcription. These complexes unwind DNA, facilitating gene regulation, DNA repair, and chromosome segregation.
Area of Science:
- Molecular Biology
- Genetics
- Chromatin Biology
Background:
- Nucleosomes act as general gene repressors, inhibiting transcription.
- Specific positive regulatory mechanisms are required to initiate transcription.
- Chromatin remodeling complexes are key to altering nucleosome structure for gene regulation.
Purpose of the Study:
- To investigate the role of RSC (remodeler- சூப்பர்காம்ப்ளெக்ஸ்) in transcription regulation.
- To elucidate the structural mechanisms by which RSC remodels nucleosomes.
- To explore additional functions of RSC in chromosomal DNA transactions.
Main Methods:
- Cryo-electron microscopy to determine the structure of RSC-nucleosome complexes.
- Genetic studies to identify additional roles of RSC.
- Biochemical assays to study DNA translocation activity.
Main Results:
- RSC creates nucleosome-free regions, positioning +1 and -1 nucleosomes.
- RSC binding perturbs nucleosome structure, unwrapping DNA.
- Cryo-EM reveals DNA interacting with RSC's charged surface, enabling ATP-dependent translocation.
- Genetic studies link RSC to DNA repair and chromosome segregation.
Conclusions:
- RSC plays a crucial role in gene transcription by remodeling nucleosomes.
- DNA unwrapping and translocation are fundamental activities of RSC.
- RSC's functions extend beyond transcription to DNA repair and chromosome segregation.
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