H3K9me-independent gene silencing in fission yeast heterochromatin by Clr5 and histone deacetylases

Autor: Geneviève Thon, Robert A. Martienssen, Jürg Bähler, Klavs R. Hansen, Janne Verhein-Hansen, Stephen Watt, Amikam Cohen, Idit Hazan, Janet F. Partridge, Sreenath Shanker
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Cancer Research
lcsh:QH426-470
Chromosomal Proteins
Non-Histone
Molecular Sequence Data
Molecular Biology/Molecular Evolution
Biology
Molecular Biology/Histone Modification
Microbiology
Methylation
Histone Deacetylases
Histones
03 medical and health sciences
Histone H3
0302 clinical medicine
Histone H1
Genetics and Genomics/Epigenetics
Gene Expression Regulation
Fungal
Heterochromatin
Histone H2A
Histone methylation
Schizosaccharomyces
Genetics
Histone code
Amino Acid Sequence
Gene Silencing
Molecular Biology/Chromatin Structure
Molecular Biology
Genetics (clinical)
Ecology
Evolution
Behavior and Systematics
030304 developmental biology
0303 health sciences
Sequence Homology
Amino Acid
Molecular Biology/Chromosome Structure
Genetics and Genomics/Gene Expression
Histone-Lysine N-Methyltransferase
Molecular Biology/Centromeres
Genetics and Genomics/Chromosome Biology
lcsh:Genetics
Histone methyltransferase
Mutation
Heterochromatin protein 1
Schizosaccharomyces pombe Proteins
Sequence Alignment
030217 neurology & neurosurgery
Mating-type region
GENOME-WIDE ANALYSIS
MATING-TYPE REGION
SCHIZOSACCHAROMYCES-POMBE
RNA INTERFERENCE
ANKYRIN REPEAT
CHROMOSOME SEGREGATION
SEXUAL-DIFFERENTIATION
EPIGENETIC INHERITANCE
REPRESS TRANSCRIPTION
MEIOTIC RECOMBINATION
Research Article
Transcription Factors
Zdroj: PLoS Genetics, Vol 7, Iss 1, p e1001268 (2011)
Hansen, K R, Hazan, I, Shanker, S, Watt, S, Hansen, J V, Bähler, J, Martienssen, R A, Partridge, J F, Cohen, A & Thon, G 2011, ' H3K9me-independent gene silencing in fission yeast heterochromatin by Clr5 and histone deacetylases ', P L o S Genetics, vol. 7, no. 1 . https://doi.org/10.1371/journal.pgen.1001268
PLOS GENET, 7 (1), Article e1001268. (2011)
PLoS Genetics
ISSN: 1553-7404
1553-7390
Popis: 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.
Author Summary In eukaryotes some histone modifications are preponderantly associated with silent chromosomal domains, however the extent to which distinct modifications contribute to the silencing of gene expression is often not known. A well-studied chromosomal domain in which histone modifications have been extensively characterized is the fission yeast mating-type region. There, histone hypo-acetylation and histone H3 lysine 9 methylation (H3K9me) are associated with a domain refractory to gene expression. Contrary to a general assumption, we found that genes naturally present in the mating-type region of wild-type strains remain repressed in the absence of the H3K9 methyltransferase Clr4. Their repression depends on histone deacetylases and on a hitherto uncharacterized factor, Clr5. Our results reveal an unsuspected robustness in the silencing mechanism, where H3K9me and deacetylation cooperate to ensure that the genes naturally present in the mating-type region remain silent in conditions where their expression would otherwise kill the cells.
Databáze: OpenAIRE
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