Dataset Information

Differential phosphorylation of Clr4^SUV39H by Cdk1 accompanies a histone H3 methylation switch that is essential for gametogenesis.

ABSTRACT: Methylation of histone H3 at lysine 9 (H3K9) is a hallmark of heterochromatin that plays crucial roles in gene silencing, genome stability, and chromosome segregation. In Schizosaccharomyces pombe, Clr4 mediates both di- and tri-methylation of H3K9. Although H3K9 methylation has been intensely studied in mitotic cells, its role during sexual differentiation remains unclear. Here, we map H3K9 methylation genome-wide during meiosis and show that constitutive heterochromatin temporarily loses H3K9me2 and becomes H3K9me3 when cells commit to meiosis. Cells lacking the ability to tri-methylate H3K9 exhibit meiotic chromosome segregation defects. Finally, the H3K9 methylation switch is accompanied by differential phosphorylation of Clr4 by the cyclin-dependent kinase Cdk1. Our results suggest that a conserved master regulator of the cell cycle controls the specificity of an H3K9 methyltransferase to prevent ectopic H3K9 methylation and to ensure faithful gametogenesis.

SUBMITTER: Kuzdere T

PROVIDER: S-EPMC9827552 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Differential phosphorylation of Clr4<sup>SUV39H</sup> by Cdk1 accompanies a histone H3 methylation switch that is essential for gametogenesis.

Kuzdere Tahsin T Flury Valentin V Schalch Thomas T Iesmantavicius Vytautas V Hess Daniel D Bühler Marc M

EMBO reports 20221121 1

Methylation of histone H3 at lysine 9 (H3K9) is a hallmark of heterochromatin that plays crucial roles in gene silencing, genome stability, and chromosome segregation. In Schizosaccharomyces pombe, Clr4 mediates both di- and tri-methylation of H3K9. Although H3K9 methylation has been intensely studied in mitotic cells, its role during sexual differentiation remains unclear. Here, we map H3K9 methylation genome-wide during meiosis and show that constitutive heterochromatin temporarily loses H3K9m ...[more]

PMID: 36408846

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Project description:Methylation of histone H3 at lysine 9 (H3K9) is a hallmark of heterochromatin that plays crucial roles in chromatin-dependent gene silencing and maintenance of genome stability by repressing repetitive DNA elements and recruiting downstream factors essential for faithful chromosome segregation. Fundamental principles of these processes have been elucidated in the fission yeast Schizosaccharomyces pombe (S. pombe), in which Clr4, the homologue of mammalian SUV39H, is the sole H3K9 methyltransferase. Although H3K9 methylation has been intensely studied in mitotic cells, occurrence and regulation during sexual differentiation remain largely unknown. Whether distinct H3 methylation states are relevant for gametogenesis is also not known. Here, using diploid S. pombe cells, we map H3K9 methylation genome-wide during the meiotic program and show that constitutive heterochromatin temporarily loses H3K9me2 and becomes H3K9me3 when cells exit mitosis and commit to the meiotic life cycle. Cells lacking the ability to tri-methylate H3K9 exhibit severe meiotic chromosome segregation defects, which does not occur in mitotic cells. Artificially increasing the affinity of the fission yeast heterochromatin protein 1 (HP1) homologue Swi6 towards H3K9me2 rescues chromosome segregation in the absence of H3K9me3. Thus, the H3K9me2 to H3K9me3 switch during early meiosis serves to retain Swi6 at centromeres, which is necessary for cohesin recruitment and kinetochore assembly. Finally, we show that the H3K9 methylation switch is regulated by differential phosphorylation of Clr4 by the cyclin-dependent kinase (CDK) Cdk1. Our results reveal how a highly conserved master regulator of the cell cycle regulates the specificity of the H3K9 methyltransferase and thereby controls the ratio of H3K9me2 to H3K9me3 to prevent unwanted gene silencing and to ensure faithful meiotic chromosome segregation. High degree of conservation of the proteins involved in our study and CDK-dependent phosphorylation of the mammalian SUV39H1 homologue suggest broad conservation of the mechanisms described here.

Dataset Information

Differential phosphorylation of Clr4^SUV39H by Cdk1 accompanies a histone H3 methylation switch that is essential for gametogenesis.

Publications

Differential phosphorylation of Clr4<sup>SUV39H</sup> by Cdk1 accompanies a histone H3 methylation switch that is essential for gametogenesis.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Differential phosphorylation of Clr4SUV39H by Cdk1 accompanies a histone H3 methylation switch that is essential for gametogenesis.

Publications

Differential phosphorylation of Clr4<sup>SUV39H</sup> by Cdk1 accompanies a histone H3 methylation switch that is essential for gametogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Differential phosphorylation of Clr4^SUV39H by Cdk1 accompanies a histone H3 methylation switch that is essential for gametogenesis.