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bioRxiv · 10.1101/2021.07.29.454039

Dual Roles for Nuclear RNAi Argonautes in C. elegans Dosage Compensation

Davis, M. B.·Chawla, B.·Jash, E.·Tushman, L. E.·Haines, R. A.·Csankovszki, G.
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Abstract

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 C. elegans. Dosage compensation in C. elegans hermaphrodites is initiated by the silencing of xol-1 and subsequent activation of the Dosage Compensation Complex (DCC) which binds to both hermaphrodite X chromosomes and reduces transcriptional output by twofold. A hallmark phenotype of dosage compensation mutants is decondensation of the X chromosomes. We characterized this phenotype in Argonaute mutants using X chromosome paint probe and fluorescence microscopy. We found that while nuclear Argonaute mutants hrde-1 and nrde-3 exhibit de-repression of xol-1 transcripts, they also effect 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 find that hrde-1 and nrde-3, together with the piRNA Argonaute prg-1, contribute to healthy dosage compensation both upstream and downstream of xol-1.

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Davis, M. B., Chawla, B., Jash, E., Tushman, L. E., Haines, R. A., Csankovszki, G.. 2021-07-29. Dual Roles for Nuclear RNAi Argonautes in C. elegans Dosage Compensation. https://doi.org/10.1101/2021.07.29.454039

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