Regulation of MORC-1 is key to the CSR-1-mediated germline gene licensing mechanism in C. elegans
The Argonaute CSR-1 is essential for germline development in C. elegans. Loss of CSR-1 leads to the downregulation of thousands of germline-expressed genes, supporting a model in which CSR-1 “licenses” gene expression via a poorly understood mechanism. In contrast, a small subset of genes is upregulated in csr-1 mutants, including morc-1, which encodes a conserved GHKL-type ATPase. We show that morc-1 is overexpressed in csr-1 mutants and accumulates over CSR-1 licensed targets, coinciding with aberrant gain of H3K9me3, reduced H3K36me3, and transcriptional repression. Strikingly, loss of morc-1 fully rescues these chromatin defects and partially restores gene expression and fertility in csr-1 mutants. Conversely, ectopic overexpression of MORC-1 in the wild-type germline is sufficient to repress CSR-1 licensed targets and severely compromise fertility. These findings support a model in which CSR-1 prevents MORC-1 overexpression and consequent misregulation of CSR-1 licensed genes. Overall design: To check if our csr-1 mutants affect CSR-1-bound sRNAs, we performed sRNA-seq of our csr-1 mutants and matched controls (control for csr-1(G560R) is N2, control for aid::csr-1 1mM auxin in aid::csr-1 0mM auxin), all samples done in triplicate.