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H3K9me2 and BRCA1 cooperate to prevent satellite repeat transcription, R-loop formation and germline sterility [ChIP-seq]

ABSTRACT: Repetitive sequences, transposable elements and silent tissue-specific genes in C. elegans are differentially enriched for di- and tri-methyl H3 lysine 9 (H3K9). SET-25 (SUV39h1/h2) catalyzes H3K9me3, while MET-2 (SetDB1) deposits only H3K9me1/me2. RNA-seq and genome-wide H3K9 methylation mapping in met-2 and set-25 single mutants showed that H3K9me2-mediated repression of satellite repeats by MET-2 correlates with germline integrity. Aberrant transcription of repeats and DNA transposons generates R-loops, loss of fertility and hydroxyurea hypersensitivity. In a genome-wide synthetic lethal screen, we identified the BRCA1 complex and factors implicated in the degradation of nuclear RNA as essential for germline integrity in met-2 mutants. Highly additive with met-2, the loss of the BRCA1 complex triggers satellite repeat transcription, generating R-loops on transcribed repeats. Supporting direct causality between satellite repeat transcription and BRCA1-mediated genome integrity, the targeted induction of MSAT1 transcripts at endogenous sites leads to damage-induced loss of fertility in wild-type C. elegans.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE100724 | GEO | 2017/07/04

SECONDARY ACCESSION(S): PRJNA392973

REPOSITORIES: GEO

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