Figure 6.—

Regulation of xol-1 through XSEs and ASEs. xol-1 is the direct molecular target of the X:A signal and integrates both X and autosomal components to determine sexual fate. The molecular diagram indicates where the XSEs act to repress xol-1 and where the ASEs function to activate xol-1. Our study showed that CEH-39 and most other XSEs communicate X chromosome dose by repressing xol-1 transcript levels. The XSE in region 1 and SEX-1 (nuclear hormone receptor) repress xol-1 through sequences in the promoter, while CEH-39 (homeodomain protein) acts through xol-1 genomic sequences that span the first three exons. CEH-39 may also function through promoter sequences. The means by which sex-2 represses xol-1 transcript levels has not been defined. Using a separate mechanism, FOX-1, an RNA-binding protein, represses xol-1 on a post-transcriptional level. Both the transcriptional and post-transcriptional mechanism are important for xol-1 repression. The ASE SEA-1 (T-box protein) activates xol-1 transcript levels using promoter sequences. XSEs and ASEs could compete directly to regulate xol-1 by binding overlapping or neighboring cis regulatory sites or indirectly by affecting components of the transcriptional machinery. The end result is that the higher XSE activity in XX animals out-competes ASE activity and inactivates xol-1, but the lower XSE activity in XO animals permits the ASE activity to activate xol-1. The high level of XOL-1 protein present in XO animals then induces the male fate, including repression of the dosage compensation machinery. The lower level of XOL-1 in XX animals permits the hermaphrodite fate, including activation of the dosage compensation machinery.