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The FACT chromatin modulator: genetic and structure/function relationships.

Richard A Singer1, Gerald C Johnston

  • 1Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Canada. richard.singer@dal.ca

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
|July 31, 2004
PubMed
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FACT, a transcription factor, helps RNA polymerase II navigate DNA by reconfiguring nucleosomes. This essential protein facilitates gene transcription by managing chromatin structure during and after DNA transit.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Chromatin structure, formed by DNA and nucleosomes, restricts access for enzymes like RNA polymerase II.
  • The FACT (Facilitates Chromatin Transcription) complex is a key regulator of transcription elongation.
  • FACT's subunits, Spt16/Cdc68 and SSRP1/Pob3, play crucial roles in nucleosome dynamics.

Purpose of the Study:

  • To elucidate the role of the FACT complex in overcoming chromatin-based transcriptional inhibition.
  • To investigate the subunit composition and functional domains of FACT, particularly in yeast.
  • To understand how FACT facilitates RNA polymerase II passage through nucleosomes.

Main Methods:

  • Genetic studies in yeast to analyze FACT mutations and functions.

Related Experiment Videos

  • Biochemical analysis of FACT subunit interactions and domain functions.
  • Investigating the role of HMG-box domains in FACT-mediated chromatin remodeling.

    • Main Results:

    • FACT actively reconfigures nucleosomes, enabling RNA polymerase II to transit DNA and thus facilitating transcription.
    • FACT also reorganizes nucleosomes post-transcription, as evidenced by mutation studies.
    • The HMG-box domain of SSRP1 is functionally substituted by Nhp6 in yeast FACT, highlighting conserved mechanisms.

    Conclusions:

    • FACT is essential for transcription elongation by dynamically managing nucleosome structure.
    • Protein unfolding and refolding are likely integral to FACT's mechanism of action.
    • Understanding FACT's role provides insights into gene regulation and chromatin dynamics.