During the UPR,
xbp-1 expression is regulated at the level of transcription, as well as through cytoplasmic splicing of its mRNA by the IRE-1 endoribonuclease. The spliced form of the
xbp-1 mRNA (
xbp-1s) encodes the transcriptionally active form of XBP-1 (XBP-1s). When SKN-1 was lacking, ER stress failed to induce accumulation of each
xbp-1 mRNA form and, remarkably, decreased the ratio of
xbp-1s to the unspliced
xbp-1 form (
xbp-1u). The
xbp-1 locus includes a predicted SKN-1 binding site (not shown), and ChIP results indicated that endogenous SKN-1 accumulates at the
xbp-1 site of transcription in response to ER stress. This evidence that SKN-1 directly regulates
xbp-1 could account for the reduction in total
xbp-1 mRNA, but not the apparent effect of SKN-1 on
xbp-1 splicing.