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bioRxiv · 10.1101/2024.11.23.624987

Multi-level transcriptional regulation of embryonic sex determination and dosage compensation by the X-signal element sex-1

Jash, E.·Tan, Z. M.·Rakozy, A. I.·Azhar, A. A.·Mendoza, H.·Csankovszki, G.
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Abstract

The C. elegans nuclear hormone receptor sex-1 is known to be an embryonic X-signal element that represses xol-1, the sex-switch gene that is the master regulator of sex determination and dosage compensation. Several prior studies on sex-1 function have suggested that sex-1 may have additional downstream roles beyond the regulation of xol-1 expression. In this study we characterize some of these additional roles of sex-1 in regulating the dual processes of sex determination and dosage compensation during embryogenesis. Our study reveals that sex-1 acts on many of the downstream targets of xol-1 in a xol-1-independent manner. Further analysis of these shared but independently regulated downstream targets uncovered that sex-1 mediates the expression of hermaphrodite- and male-biased genes during embryogenesis. We validated sex-1 binding on one of these downstream targets, the male-developmental gene her-1. Our data suggests a model where sex-1 exhibits multi-level direct transcriptional regulation on several targets, including xol-1 and genes downstream of xol-1, to reinforce the appropriate expression of sex-biased transcripts in XX embryos. Furthermore, we found that xol-1 sex-1 double mutants show defects in dosage compensation. Our study provides evidence that misregulation of dpy-21, one of the components of the dosage compensation complex, and the subsequent misregulation of H4K20me1 enrichment on the X chromosomes, may contribute to this defect.

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Jash, E., Tan, Z. M., Rakozy, A. I., Azhar, A. A., Mendoza, H., Csankovszki, G.. 2024-11-24. Multi-level transcriptional regulation of embryonic sex determination and dosage compensation by the X-signal element sex-1. https://doi.org/10.1101/2024.11.23.624987

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