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

The Caenorhabditis elegans nuclear hormone receptor sex-1 is 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 multilevel 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.