Two parallel pathways recruit the H3K9me3 HMT in somatic cells, requiring the Argonaut NRDE-3, or the MBT-domain protein, LIN-61 (smallRNA-seq)

ABSTRACT: The establishment and maintenance of chromatin domains shape the epigenetic memory of a cell, with histone H3 lysine 9 methylation defining repressed heterochromatin. We show that in C. elegans the SET-25 (SUV39/G9a) HMT that catalyzes H3K9me1-3, is able to establish repressed domains de novo. We identify here two distinct pathways that recruit SET-25 to its targets. One requires LIN-61 (L3MBTL2), a conserved protein with 4 MBT domains that recognizes H3K9me2 deposited by the HMT MET-2 (SETDB1). The second pathway is MET-2-independent and requires a somatic Argonaut NRDE-3 and 22nt small nuclear RNAs. This NRDE-3 pathway targets ~10% of all SET-25-modified loci genome-wide including intact RNA and DNA transposons. Removal of both pathways in the met-2;nrde-3 double mutant synergistically derepresses transposons in early embryos and elevates embryonic lethality. The redundancy of these pathways illustrates the key role played by chromatin-mediated silencing in protecting the genome against inherent threats.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE156550 | GEO | 2020/12/01

REPOSITORIES: GEO