Kirshner Jessica A, Picard Colette L, Weiser Natasha E, Mehta Nicita, Feng Suhua, Murphy Victoria N, Vakhnovetsky Anna, Alessi Amelia F, Xiao Connie, Inoki Kai, El Mouridi Sonia, Frøkjær-Jensen Christian, Jacobsen Steven E, Kim John K
Department of Biology, The Johns Hopkins University, Baltimore, MD, USA.
Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
Sci Adv. 2025 Jun 20;11(25):eado4170. doi: 10.1126/sciadv.ado4170.
The Argonaute CSR-1 is essential for germline development in . 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 mutants, including , which encodes a conserved GHKL-type ATPase. We show that is overexpressed in mutants and accumulates over CSR-1 licensed targets, coinciding with aberrant gain of H3K9me3, reduced H3K36me3, and transcriptional repression. Notably, loss of fully rescues these chromatin defects and partially restores gene expression and fertility in 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.
AGO蛋白CSR-1对[生物名称]的生殖系发育至关重要。CSR-1的缺失导致数千个生殖系表达基因的下调，支持了一种模型，即CSR-1通过一种尚不清楚的机制“许可”基因表达。相比之下，一小部分基因在[突变体名称]突变体中上调，包括[基因名称]，它编码一种保守的GHKL型ATP酶。我们发现[基因名称]在[突变体名称]突变体中过表达，并在CSR-1许可的靶标上积累，同时伴随着H3K9me3的异常增加、H3K36me3的减少以及转录抑制。值得注意的是，[基因名称]的缺失完全挽救了这些染色质缺陷，并部分恢复了[突变体名称]突变体中的基因表达和生育力。相反，在野生型生殖系中异位过表达MORC-1足以抑制CSR-1许可的靶标并严重损害生育力。这些发现支持了一种模型，即CSR-1可防止MORC-1过表达以及随后对CSR-1许可基因的错误调控。
