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Published on: September 20, 2018
SHREC, an effector complex for heterochromatic transcriptional silencing
Tomoyasu Sugiyama1, Hugh P Cam, Rie Sugiyama
1Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|February 10, 2007
Summary
A novel protein complex, SHREC, mediates transcriptional gene silencing in fission yeast heterochromatin. This complex regulates nucleosome positioning to establish higher-order chromatin structures essential for gene silencing.
Area of Science:
- Epigenetics
- Molecular Biology
- Chromatin Biology
Background:
- Heterochromatin is traditionally associated with transcriptional gene silencing (TGS).
- Recent findings in fission yeast suggest a role for RNAi-mediated posttranscriptional gene silencing (PTGS) in heterochromatin, challenging the primacy of TGS.
- The precise molecular mechanisms underlying heterochromatic TGS remain incompletely understood.
Purpose of the Study:
- To identify and characterize the molecular machinery responsible for heterochromatic transcriptional gene silencing in fission yeast.
- To elucidate the composition and function of the effector complex mediating TGS at heterochromatin.
- To investigate the recruitment mechanisms and regulatory roles of this complex in chromatin organization.
Main Methods:
- Biochemical purification and characterization of protein complexes from fission yeast.
- Genetic analysis to assess the function of identified proteins in gene silencing.
- Chromatin immunoprecipitation and localization studies to determine complex distribution.
- Nucleosome positioning assays and analysis of higher-order chromatin structures.
Main Results:
- Identification of the SHREC (Silencing Hub and REgulatory Complex) as a multienzyme effector complex mediating heterochromatic TGS.
- SHREC comprises a core quartet (Clr1, Clr2, Clr3, Mit1) distributed across heterochromatin domains.
- SHREC utilizes histone deacetylase (Clr3) and chromatin remodeler (Mit1) activities to establish TGS and regulates nucleosome positioning for higher-order chromatin assembly.
- SHREC is recruited to telomeres via Ccq1/Taz1 and RNAi machinery, and to euchromatic sites through Swi6/HP1-dependent mechanisms.
Conclusions:
- SHREC is a key effector complex for transcriptional gene silencing in fission yeast heterochromatin.
- The complex's activities, including nucleosome positioning regulation, are critical for establishing functional heterochromatin.
- SHREC integrates distinct recruitment pathways to ensure its localization and function across different genomic regions.
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