Sir2 regulates histone H3 lysine 9 methylation and heterochromatin assembly in fission yeast

Shankaranarayana, G. D., Motamedi, M. R., Moazed, D., Grewal, S. I. (2003) Sir2 regulates histone H3 lysine 9 methylation and heterochromatin assembly in fission yeast. Current Biology, 13 (14). pp. 1240-6. ISSN 0960-9822

URL: http://www.ncbi.nlm.nih.gov/pubmed/12867036
DOI: 10.1016/S0960-9822(03)00489-5

Abstract

Hypoacetylated histones are a hallmark of heterochromatin in organisms ranging from yeast to humans. Histone deacetylation is carried out by both NAD(+)-dependent and NAD(+)-independent enzymes. In the budding yeast Saccharomyces cerevisiae, deacetylation of histones in heterochromatic chromosomal domains requires Sir2, a phylogenetically conserved NAD(+)-dependent deacetylase. In the fission yeast Schizosaccharomyces pombe, NAD(+)-independent histone deacetylases are required for the formation of heterochromatin, but the role of Sir2-like deacetylases in this process has not been evaluated. Here, we show that spSir2, the S. pombe Sir2-like protein that is the most closely related to the S. cerevisiae Sir2, is an NAD(+)-dependent deacetylase that efficiently deacetylates histone H3 lysine 9 (K9) and histone H4 lysine 16 (K16) in vitro. In sir2 Delta cells, silencing at the donor mating-type loci, telomeres, and the inner centromeric repeats (imr) is abolished, while silencing at the outer centromeric repeats (otr) and rDNA is weakly reduced. Furthermore, Sir2 is required for hypoacetylation and methylation of H3-K9 and for the association of Swi6 with the above loci in vivo. Our findings suggest that the NAD(+)-dependent deacetylase Sir2 plays an important and conserved role in heterochromatin assembly in eukaryotes.

Item Type: Paper
Uncontrolled Keywords: Acetylation Chromosomal Proteins, Non-Histone/metabolism Chromosome Mapping Comparative Study Gene Silencing Heterochromatin/ metabolism Histones/ metabolism Lysine/ metabolism Methylation Methyltransferases Polymerase Chain Reaction Precipitin Tests Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Schizosaccharomyces Schizosaccharomyces pombe Proteins/metabolism Sirtuins/ metabolism Staining and Labeling
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > histone
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation > histone methylation
organism description > yeast
CSHL Authors:
Communities: CSHL labs > Grewal lab
Depositing User: Matt Covey
Date Deposited: 11 Jun 2013 16:50
Last Modified: 11 Jun 2013 16:50
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27957

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