Regulation of MORC-1 is key to the CSR-1-mediated germline gene licensing mechanism in <i>C. elegans</i>.

Abstract

The Argonaute CSR-1 is essential for germline development in <i>C. elegans</i>. Loss of CSR-1 leads to the down-regulation 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 up-regulated in <i>csr-1</i> mutants, including <i>morc-1</i>, which encodes a conserved GHKL-type ATPase. We show that <i>morc-1</i> is overexpressed in <i>csr-1</i> mutants and accumulates over CSR-1 licensed targets, coinciding with aberrant gain of H3K9me3, reduced H3K36me3, and transcriptional repression. Notably, loss of <i>morc-1</i> fully rescues these chromatin defects and partially restores gene expression and fertility in <i>csr-1</i> mutants. Conversely, ectopic overexpression of MORC-1 in the wild-type germ line 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.