1. S. pombe LSD1 Homologs Regulate Heterochromatin Propagation and Euchromatic Gene Transcription
- Author
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Robert A. Martienssen, Fei Lan, Danesh Moazed, Yujiang Shi, Yang Shi, Maite Huarte, Steven P. Gygi, Matthew W. Vaughn, Judit Villén, André Verdel, Mikel Zaratiegui, Department of pathology, Harvard Medical School [Boston] (HMS), Cold Spring Harbor Laboratory (CSHL), Department of cell biology, and Verdel, Andre
- Subjects
Transcription, Genetic ,Euchromatin ,MESH: Sequence Homology, Amino Acid ,Cell Survival ,Heterochromatin ,MESH: Oxidoreductases, N-Demethylating ,Molecular Sequence Data ,MESH: Amino Acid Sequence ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Biology ,Histones ,MESH: DNA Methylation ,Gene Expression Regulation, Fungal ,Schizosaccharomyces ,Demethylase activity ,Amino Acid Sequence ,Epigenetics ,Molecular Biology ,MESH: Histones ,Genetics ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Molecular Sequence Data ,Sequence Homology, Amino Acid ,MESH: Transcription, Genetic ,EZH2 ,MESH: Schizosaccharomyces pombe Proteins ,Oxidoreductases, N-Demethylating ,Promoter ,Cell Biology ,DNA Methylation ,MESH: Schizosaccharomyces ,MESH: Heterochromatin ,Histone ,MESH: Cell Survival ,MESH: Euchromatin ,MESH: Genome, Fungal ,biology.protein ,Heterochromatin protein 1 ,Schizosaccharomyces pombe Proteins ,Genome, Fungal ,MESH: Gene Expression Regulation, Fungal - Abstract
International audience; LSD1 represses and activates transcription by demethylating histone H3K4me and H3K9me, respectively. Genetic ablation of the S. pombe homologs, splsd1 and splsd2, resulted in slow growth and lethality, respectively, underscoring their physiological importance. spLsd1 and spLsd2 form a stable protein complex, which exhibits demethylase activity toward methylated H3K9 in vitro. Both proteins were associated with the heterochromatin boundary regions and euchromatic gene promoters. Loss of spLsd1 resulted in increased H3K9 methylation accompanied by reduced euchromatic gene transcription and heterochromatin propagation. Removal of the H3K9 methylase Clr4 partially suppressed the slow growth phenotype of splsd1Delta. Conversely, catalytically inactivating point mutations in the splsd1 and splsd2 genes partially mimicked the growth and heterochromatin propagation phenotypes. Taken together, these findings suggest the importance of both enzymatic and nonenzymatic roles of spLsd1 in regulating heterochromatin propagation and euchromatic transcription and also suggest that misregulation of spLsd1/2 is likely to impact the epigenetic state of the cell.
- Published
- 2007
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