UPR factors required for ER stress-induced SKN-1 activation.

<p>(A) ER stress-induced activation of <i>skn-1</i> and its target genes requires core UPR factors. RNA levels were assayed by qRT-PCR after RNAi against core UPR genes or in core UPR factor mutants (indicated by ^M) after TM treatment. (B-E) IRE-1 is required for ER stress-induced SKN-1 accumulation and activity at SKN-1 target genes <i>gst-4</i> and <i>pcp-2</i>. Presence of SKN-1 and transcription markers was assayed by ChIP as in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003701#pgen-1003701-g002" target="_blank">Figure 2</a>, and <i>ire-1</i> was knocked down by RNAi. (F–H) Endogenous XBP-1 (F), ATF-6 (G), and SKN-1 (H) bind within the <i>skn-1</i> gene locus in response to TM-induced ER stress, with binding assayed by ChIP. Multiple start sites are noted within the <i>skn-1</i> locus. Error bars represent SEM, and * p≤.05, ** p≤.01, *** p≤.001 by student's t-test, relative to <i>pL4440</i> Control unless otherwise indicated. See also <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003701#pgen.1003701.s005" target="_blank">Figure S5</a>.