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PMID: 19014414 Published · epublish English Journal Article

The fungus Neurospora crassa displays telomeric silencing mediated by multiple sirtuins and by methylation of histone H3 lysine 9.

Epigenetics & chromatin ·Vol. 1 ·No. 1 ·2008-11-03 ·Pages 5

Smith KM, Kothe GO, Matsen CB, Khlafallah TK, Adhvaryu KK, Hemphill M, Freitag M, Motamedi MR, Selker EU

Abstract

Silencing of genes inserted near telomeres provides a model to investigate the function of heterochromatin. We initiated a study of telomeric silencing in Neurospora crassa, a fungus that sports DNA methylation, unlike most other organisms in which telomeric silencing has been characterized. The selectable marker, hph, was inserted at the subtelomere of Linkage Group VR in an nst-1 (neurospora sir two-1) mutant and was silenced when nst-1 function was restored. We show that NST-1 is an H4-specific histone deacetylase. A second marker, bar, tested at two other subtelomeres, was similarly sensitive to nst-1 function. Mutation of three additional SIR2 homologues, nst-2, nst-3 and nst-5, partially relieved silencing. Two genes showed stronger effects: dim-5, which encodes a histone H3 K9 methyltransferase and hpo, which encodes heterochromatin protein-1. Subtelomeres showed variable, but generally low, levels of DNA methylation. Elimination of DNA methylation caused partial derepression of one telomeric marker. Characterization of histone modifications at subtelomeric regions revealed H3 trimethyl-K9, H3 trimethyl-K27, and H4 trimethyl-K20 enrichment. These modifications were slightly reduced when telomeric silencing was compromised. In contrast, acetylation of histones H3 and H4 increased. We demonstrate the presence of telomeric silencing in Neurospora and show a dependence on histone deacetylases and methylation of histone H3 lysine 9. Our studies also reveal silencing functions for DIM-5 and HP1 that appear independent of their role in de novo DNA methylation.

Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Smith Kristina M
Institute of Molecular Biology and Department of Biology, University of Oregon, Eugene, OR 97403, USA.
Kothe Gregory O
Institute of Molecular Biology and Department of Biology, University of Oregon, Eugene, OR 97403, USA.
Matsen Cindy B
Institute of Molecular Biology and Department of Biology, University of Oregon, Eugene, OR 97403, USA.
Khlafallah Tamir K
Institute of Molecular Biology and Department of Biology, University of Oregon, Eugene, OR 97403, USA.
Adhvaryu Keyur K
Institute of Molecular Biology and Department of Biology, University of Oregon, Eugene, OR 97403, USA.
Hemphill Melissa
Institute of Molecular Biology and Department of Biology, University of Oregon, Eugene, OR 97403, USA.
Freitag Michael
Institute of Molecular Biology and Department of Biology, University of Oregon, Eugene, OR 97403, USA.
Motamedi Mohammad R
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Selker Eric U
Institute of Molecular Biology and Department of Biology, University of Oregon, Eugene, OR 97403, USA.
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Article Info
Journal
Epigenetics & chromatin
Abbr.
Epigenetics Chromatin
ISSN
1756-8935
DOI
10.1186/1756-8935-1-5
Published
2008-11-03
Epub
2008-00-03
Pages
5
Language
English
Region
England
NLM ID
101471619
PMCID
PMC2596135
Grants
NIGMS NIH HHS · R01 GM061641 · United States
External Links
PubMed source DOI: 10.1186/1756-8935-1-5 PMC Full Text View journal details
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