Reference - PMID:38815580 - RNA quality control factors nucleate Clr4/SUV39H and trigger constitutive heterochromatin assembly.
Reference summary
- PubMed ID
- PMID:38815580
- Title
- RNA quality control factors nucleate Clr4/SUV39H and trigger constitutive heterochromatin assembly.
- Authors
- Khanduja JS, Joh RI, Perez MM, Paulo JA, Palmieri CM, Zhang J, Gulka AOD, Haas W, Gygi SP, Motamedi M
- Citation
- Cell 2024 May 21;
- Publication year
- 2024
- Abstract
- In eukaryotes, the Suv39 family of proteins tri-methylate lysine 9 of histone H3 (H3K9me) to form constitutive heterochromatin. However, how Suv39 proteins are nucleated at heterochromatin is not fully described. In the fission yeast, current models posit that Argonaute1-associated small RNAs (sRNAs) nucleate the sole H3K9 methyltransferase, Clr4/SUV39H, to centromeres. Here, we show that in the absence of all sRNAs and H3K9me, the Mtl1 and Red1 core (MTREC)/PAXT complex nucleates Clr4/SUV39H at a heterochromatic long noncoding RNA (lncRNA) at which the two H3K9 deacetylases, Sir2 and Clr3, also accumulate by distinct mechanisms. Iterative cycles of H3K9 deacetylation and methylation spread Clr4/SUV39H from the nucleation center in an sRNA-independent manner, generating a basal H3K9me state. This is acted upon by the RNAi machinery to augment and amplify the Clr4/H3K9me signal at centromeres to establish heterochromatin. Overall, our data reveal that lncRNAs and RNA quality control factors can nucleate heterochromatin and function as epigenetic silencers in eukaryotes.
