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PMID: 11387218 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A role for DNA polymerase alpha in epigenetic control of transcriptional silencing in fission yeast.

The EMBO journal ·Vol. 20 ·No. 11 ·2001-06-01 ·Pages 2857-66

Nakayama Ji, Allshire RC, Klar AJ, Grewal SI

Abstract

In the fission yeast Schizosaccharomyces pombe, transcriptional silencing at the mating-type region, centromeres and telomeres is epigenetically controlled, and results from the assembly of higher order chromatin structures. Chromatin proteins associated with these silenced loci are believed to serve as molecular bookmarks that help promote inheritance of the silenced state during cell division. Specifically, a chromodomain protein Swi6 is believed to be an important determinant of the epigenetic imprint. Here, we show that a mutation in DNA polymerase alpha (pol(alpha)) affects Swi6 localization at the mating-type region and causes a 45-fold increase in spontaneous transition from the silenced epigenetic state to the expressed state. We also demonstrate that pol(alpha) mutant cells are defective in Swi6 localization at centromeres and telomeres. Genetic analysis suggests that Polalpha and Swi6 are part of the same silencing pathway. Interestingly, we found that Swi6 directly binds to Pol(alpha) in vitro. Moreover, silencing-defective mutant Pol(alpha) displays reduced binding to Swi6 protein. This work indicates involvement of a DNA replication protein, Pol(alpha), in heterochromatin assembly and inheritance of epigenetic chromatin structures.

MeSH Terms
Amino Acid Sequence Animals Chromatin/metabolism Chromosomal Proteins, Non-Histone/metabolism Conserved Sequence DNA Polymerase I/chemistry,genetics,metabolism Fungal Proteins/chemistry,metabolism Gene Expression Regulation, Fungal Gene Silencing Humans Molecular Sequence Data Restriction Mapping Saccharomyces cerevisiae Proteins Schizosaccharomyces/enzymology,genetics Sequence Alignment Sequence Homology, Amino Acid Transcription Factors/chemistry,metabolism Transcription, Genetic
Chemicals
Chromatin Chromosomal Proteins, Non-Histone Fungal Proteins SWI6 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcription Factors DNA Polymerase I
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Nakayama Ji
Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, NY 11724, National Cancer Institute, Frederick, MD, USA and MRC Human Genetics Unit, Edinburgh, UK.
Allshire R C
Klar A J
Grewal S I
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.11.2857
Published
2001-06-01
Pages
2857-66
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125490
Subset
IM
Grants
NIGMS NIH HHS · R01 GM059772 · United States
NIGMS NIH HHS · R01 GM59772-02 · United States
External Links
PubMed source DOI: 10.1093/emboj/20.11.2857 PMC Full Text View journal details
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