RRC ID 65361
Author Padeken J, Methot S, Zeller P, Delaney CE, Kalck V, Gasser SM.
Title Argonaute NRDE-3 and MBT domain protein LIN-61 redundantly recruit an H3K9me3 HMT to prevent embryonic lethality and transposon expression.
Journal Genes Dev
Abstract The establishment and maintenance of chromatin domains shape the epigenetic memory of a cell, with the methylation of histone H3 lysine 9 (H3K9me) defining transcriptionally silent heterochromatin. We show here that the C. elegans SET-25 (SUV39/G9a) histone methyltransferase (HMT), which catalyzes H3K9me1, me2 and me3, can establish repressed chromatin domains de novo, unlike the SETDB1 homolog MET-2. Thus, SET-25 is needed to silence novel insertions of RNA or DNA transposons, and repress tissue-specific genes de novo during development. We identify two partially redundant pathways that recruit SET-25 to its targets. One pathway requires LIN-61 (L3MBTL2), which uses its four MBT domains to bind the H3K9me2 deposited by MET-2. The second pathway functions independently of MET-2 and involves the somatic Argonaute NRDE-3 and small RNAs. This pathway targets primarily highly conserved RNA and DNA transposons. These redundant SET-25 targeting pathways (MET-2-LIN-61-SET-25 and NRDE-3-SET-25) ensure repression of intact transposons and de novo insertions, while MET-2 can act alone to repress simple and satellite repeats. Removal of both pathways in the met-2;nrde-3 double mutant leads to the loss of somatic H3K9me2 and me3 and the synergistic derepression of transposons in embryos, strongly elevating embryonic lethality.
Volume 35(1-2)
Pages 82-101
Published 2021-1-1
DOI 10.1101/gad.344234.120
PII gad.344234.120
PMID 33303642
PMC PMC7778263
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism* DNA Transposable Elements / genetics* Embryo, Nonmammalian Gene Expression Regulation / genetics* Gene Silencing Heterochromatin / genetics* Heterochromatin / metabolism Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism Histones / metabolism Methylation Mutation RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism*
Resource
C.elegans tm2649 tm1116