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H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases

Hansen, KR; Hazan, I; Shanker, S; Watt, S; Verhein-Hansen, J; Bahler, J; Martienssen, RA; ... Thon, G; + view all (2011) H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases. PLOS GENET , 7 (1) , Article e1001268. 10.1371/journal.pgen.1001268. Green open access

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Abstract

Nucleosomes in heterochromatic regions bear histone modifications that distinguish them from euchromatic nucleosomes. Among those, histone H3 lysine 9 methylation (H3K9me) and hypoacetylation have been evolutionarily conserved and are found in both multicellular eukaryotes and single-cell model organisms such as fission yeast. In spite of numerous studies, the relative contributions of the various heterochromatic histone marks to the properties of heterochromatin remain largely undefined. Here, we report that silencing of the fission yeast mating-type cassettes, which are located in a well-characterized heterochromatic region, is hardly affected in cells lacking the H3K9 methyltransferase Clr4. We document the existence of a pathway parallel to H3K9me ensuring gene repression in the absence of Clr4 and identify a silencing factor central to this pathway, Clr5. We find that Clr5 controls gene expression at multiple chromosomal locations in addition to affecting the mating-type region. The histone deacetylase Clr6 acts in the same pathway as Clr5, at least for its effects in the mating-type region, and on a subset of other targets, notably a region recently found to be prone to neo-centromere formation. The genomic targets of Clr5 also include Ste11, a master regulator of sexual differentiation. Hence Clr5, like the multi-functional Atf1 transcription factor which also modulates chromatin structure in the mating-type region, controls sexual differentiation and genome integrity at several levels. Globally, our results point to histone deacetylases as prominent repressors of gene expression in fission yeast heterochromatin. These deacetylases can act in concert with, or independently of, the widely studied H3K9me mark to influence gene silencing at heterochromatic loci.

Type: Article
Title: H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.1001268
Publisher version: http://dx.doi.org/10.1371/journal.pgen.1001268
Language: English
Additional information: © 2011 Hansen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The reported research was supported by the Danish Research Council (FNU 09-064065 to KRH and FNU 272-07-0599 to GT), the Lundbeck Foundation (R9-A867 to GT), the University of Copenhagen Center of Excellence MolPhysX (to GT), The Israel Science Foundation (grant 438/04 to AC), Cancer Research UK (to JB), R01GM076396 (to RAM), R01GM084045 (to JFP), the NIH/NCI Cancer Center Core Support (5 P30 CA 021765-32 to JFP), and the American Lebanese Syrian Associated Charities (ALSAC) (to JFP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: GENOME-WIDE ANALYSIS, MATING-TYPE REGION, SCHIZOSACCHAROMYCES-POMBE, RNA INTERFERENCE, ANKYRIN REPEAT, CHROMOSOME SEGREGATION, SEXUAL-DIFFERENTIATION, EPIGENETIC INHERITANCE, REPRESS TRANSCRIPTION, MEIOTIC RECOMBINATION
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/763510
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