The Fungus Neurospora Crassa Displays Telomeric Silencing Mediated by Multiple Sirtuins and by Methylation of Histone H3 Lysine 9

Overview

Journal Epigenetics Chromatin

Publisher Biomed Central

Specialties Biochemistry
Genetics

Date 2008 Nov 19

PMID 19014414

Citations 45

Authors

Kristina M Smith

Gregory O Kothe

Cindy B Matsen

Tamir K Khlafallah

Keyur K Adhvaryu

Melissa Hemphill

Michael Freitag

Mohammad R Motamedi

Eric U Selker

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Results: 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.

Conclusion: 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.

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