Regulation of MORC-1 is key to the CSR-1–mediated germline gene licensing mechanism in C. elegans
- Jessica A. Kirshner
- Colette L. Picard
- Natasha E. Weiser
- Nicita Mehta
- Suhua Feng
- Victoria N. Murphy
- Anna Vakhnovetsky
- Amelia F. Alessi
- Connie Xiao
- Kai Inoki
- Sonia El Mouridi
- Christian Frøkjær-Jensen
- Steven E. Jacobsen
- John K. Kim
2025-06-20
The Argonaute CSR-1 is essential for germline development in C. elegans . 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 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. Notably, 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 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.