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FACT facilitates transcription-dependent nucleosome alteration
Rimma Belotserkovskaya1, Sangtaek Oh, Vladimir A Bondarenko
1Howard Hughes Medical Institute, Department of Biochemistry, Division of Nucleic Acids Enzymology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
The FACT complex facilitates RNA polymerase II transcription through nucleosomes by removing histone dimers. This complex also deposits histones, maintaining chromatin structure during gene expression.
Area of Science:
- Molecular Biology
- Epigenetics
- Chromatin Dynamics
Background:
- Chromatin, the complex of DNA and proteins, presents a barrier to transcription.
- The FACT (facilitates chromatin transcription) complex is known to be essential for transcript elongation by RNA polymerase II (Pol II).
Purpose of the Study:
- To elucidate the mechanism by which the FACT complex facilitates transcription through nucleosomes.
- To investigate the histone chaperone activity of the FACT complex.
Main Methods:
- In vitro transcription assays using purified FACT complex and nucleosomal DNA.
- Biochemical analyses to assess histone removal and deposition activities.
Main Results:
- FACT destabilizes nucleosomal structure, enabling Pol II passage by removing one histone H2A-H2B dimer.
- FACT exhibits intrinsic histone chaperone activity, capable of depositing core histones onto DNA.
- FACT's activity is dependent on both its subunits and the acidic C-terminus of Spt16.
Conclusions:
- FACT plays a dual role in transcription: facilitating passage through nucleosomes and maintaining histone integrity.
- The mechanism involves dynamic nucleosome remodeling and histone management, preserving epigenetic information.
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