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. 2014 Dec 28;290(7):4367–4382. doi: 10.1074/jbc.M114.605022

FIGURE 6.

FIGURE 6.

Enhancement of bmal1b expression by Per2 is evolutionally conserved between zebrafish and mice. A, roles of RORα, REV-ERBα, PER2, and RORE in Bmal1 transcription. RORα activates Bmal1 transcription, whereas REV-ERBα competes with RORα to repress Bmal1 expression. Mouse PER2 reverses the inhibitory effect of REV-ERBα on RORα-mediated Bmal1 transcription. All effects are lost without the two RORE motifs. B, mouse PER2 alone cannot reverse the repressive effect of REV-ERBα on Bmal1 expression. C, mouse PER2 enhances RORα-mediated Bmal1 transcription with the presence of RORα. D, mouse PER2 enhances zebrafish Rorαa- or zebrafish Rorαb-mediated zebrafish bmal1b transcription. E, zebrafish Per2 enhances mouse RORα-mediated mouse Bmal1 transcription. F, zebrafish Per2 cannot reverse the inhibitory effect of mouse REV-ERBα on RORα-mediated Bmal1 transcription. Zebrafish Rev-erbα cannot outcompete mouse RORα nor can zebrafish Rev-erbα repress mouse Bmal1 transcription. G, mouse PER2 cannot reverse the inhibitory effect of zebrafish Rev-erbα on Rorαa-mediated bmal1b transcription; however, mouse REV-ERBα can outcompete zebrafish Rorαa to repress zebrafish bmal1b transcription. H, cross-transfection experiments showing that zebrafish Rev-erbα significantly inhibits mouse Bmal1 expression without the presence of RORα. ***, p < 0.001; NS, not significant. Error bars represent S.E.