4.4 Article

Dual roles for nuclear RNAi Argonautes in Caenorhabditis elegans dosage compensation

Journal

GENETICS
Volume 221, Issue 1, Pages -

Publisher

GENETICS SOCIETY AMERICA
DOI: 10.1093/genetics/iyac033

Keywords

nuclear RNAi; Argonautes; dosage compensation; Caenorhabditis elegans; chromatin structure; gene regulation; development; X-linked gene expression; FISH

Funding

  1. National Institute of General Medical Sciences [NIH R01GM13385801]
  2. Michigan Predoctoral Training in Genetics [T32 GM007544]
  3. Edwards Fellowship
  4. Okkleberg Fellowship from the Department of MCDB at the University of Michigan
  5. National Institute of Health Office of Research Infrastructure Programs [P40 OD010440]

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Dosage compensation is a crucial gene regulatory mechanism that affects chromatin structure and is essential for organismal health. In this study, Argonaute genes were identified as promoters of dosage compensation in Caenorhabditis elegans. These genes not only impact gene expression but also influence the condensation of the X chromosomes.
Dosage compensation involves chromosome-wide gene regulatory mechanisms which impact higher order chromatin structure and are crucial for organismal health. Using a genetic approach, we identified Argonaute genes which promote dosage compensation in Caenorhabditis elegans. Dosage compensation in C. elegans hermaphrodites is initiated by the silencing of xol-1 and subsequent activation of the dosage compensation complex which binds to both hermaphrodite X chromosomes and reduces transcriptional output by half. A hallmark phenotype of dosage compensation mutants is decondensation of the X chromosomes. We characterized this phenotype in Argonaute mutants using X chromosome paint probes and fluorescence microscopy. We found that while nuclear Argonaute mutants hrde-1 and nrde-3, as well as mutants for the piRNA Argonaute prg-1, exhibit derepression of xol-1 transcripts, they also affect X chromosome condensation in a xol-1-independent manner. We also characterized the physiological contribution of Argonaute genes to dosage compensation using genetic assays and found that hrde-1 and nrde-3 contribute to healthy dosage compensation both upstream and downstream of xol-1.

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