%0 Journal Article
%T RNA quality control factors nucleate Clr4/SUV39H and trigger constitutive heterochromatin assembly.
%A Khanduja JS
%A Joh RI
%A Perez MM
%A Paulo JA
%A Palmieri CM
%A Zhang J
%A Gulka AOD
%A Haas W
%A Gygi SP
%A Motamedi M
%J Cell
%V 187
%N 13
%D 2024 Jun 20
%M 38815580
%F 66.85
%R 10.1016/j.cell.2024.04.042
%X 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.