Distinct roles for Sir2 and RNAi in centromeric heterochromatin nucleation, spreading and maintenance
| Autor: | Robin C. Allshire, Georgina L. Hamilton, Pauline N. C. B. Audergon, Alessia Buscaino, Erwan Lejeune, Alison L. Pidoux |
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| Rok vydání: | 2013 |
| Předmět: |
Euchromatin
Heterochromatin Neuroscience(all) Article General Biochemistry Genetics and Molecular Biology Chromodomain 03 medical and health sciences 0302 clinical medicine RNA interference Immunology and Microbiology(all) Centromere Nucleosome Molecular Biology 030304 developmental biology Genetics 0303 health sciences epigenetics General Immunology and Microbiology biology Biochemistry Genetics and Molecular Biology(all) General Neuroscience fungi heterochromatin HDACs centromeres Cell biology Histone RNAi biology.protein Heterochromatin protein 1 030217 neurology & neurosurgery |
| Zdroj: | The EMBO Journal Buscaino, A, Lejeune, E, Audergon, P, Hamilton, G, Pidoux, A & Allshire, R C 2013, ' Distinct roles for Sir2 and RNAi in centromeric heterochromatin nucleation, spreading and maintenance ', EMBO Journal, vol. 32, no. 9, pp. 1250-1264 . https://doi.org/10.1038/emboj.2013.72 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1038/emboj.2013.72 |
| Popis: | Epigenetically regulated heterochromatin domains govern essential cellular activities. A key feature of heterochromatin domains is the presence of hypoacetylated nucleosomes, which are methylated on lysine 9 of histone H3 (H3K9me). Here, we investigate the requirements for establishment, spreading and maintenance of heterochromatin using fission yeast centromeres as a paradigm. We show that establishment of heterochromatin on centromeric repeats is initiated at modular ‘nucleation sites' by RNA interference (RNAi), ensuring the mitotic stability of centromere-bearing minichromosomes. We demonstrate that the histone deacetylases Sir2 and Clr3 and the chromodomain protein Swi6HP1 are required for H3K9me spreading from nucleation sites, thus allowing formation of extended heterochromatin domains. We discovered that RNAi and Sir2 along with Swi6HP1 operate in two independent pathways to maintain heterochromatin. Finally, we demonstrate that tethering of Sir2 is pivotal to the maintenance of heterochromatin at an ectopic locus in the absence of RNAi. These analyses reveal that Sir2, together with RNAi, are sufficient to ensure heterochromatin integrity and provide evidence for sequential establishment, spreading and maintenance steps in the assembly of centromeric heterochromatin. Distinct roles for Sir2 and RNAi in centromeric heterochromatin nucleation, spreading and maintenance Sir2 and Clr3 histone deacetylases allow spreading of repressive histone methylation from RNAi-dependent nucleation sites, explaining the previously enigmatic role of Sir2 in fission yeast centromere silencing. |
| Databáze: | OpenAIRE |
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