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. Author manuscript; available in PMC: 2020 Nov 4.
Published in final edited form as: Nat Neurosci. 2020 May 4;23(6):718–729. doi: 10.1038/s41593-020-0627-5

Figure 4. Adar1-Z-DNA interaction at the Nrxn3 locus modulates the expression of transcripts derived from a non-coding region enriched with SINEs.

Figure 4.

a, Model depicting the recognition and resolution of Z-DNA by Adar1 binding b, There was a significant reduction in Z-DNA when comparing fear-trained animals exposed to a novel context following fear conditioning (retention control: RC) to those fear-conditioned followed by 10CS (EXT 10), 30CS (EXT 30), or 60CS extinction (EXT 60) for the Nrxn3 locus (n = 5–8 animals per group from a single cohort, ANOVA F3,23 = 39.48 ****p<0.0001, Dunnett’s post-hoc tests: RC vs EXT 10 p = 0.0879 RC vs EXT 30 ****p <0.0001, RC vs EXT 60 ****p<0.0001). Further there was a significant increase in c, Adar1 at the 30 CS EXT time point (n = 5–8 animals per group from a single cohort, ANOVA F3,23 = 8.130 ***p<0.001, Dunnett’s post-hoc tests: RC vs EXT 10 p = 0.9993 RC vs EXT 30 ****p <0.0001, RC vs EXT 60 p > 0.9999). d, In response to extinction training, the Nrxn3 transcript was significantly decreased (n = 5–8 animals per group from a single cohort, ANOVA, F3,18 = 4.636 *p<0.01, Dunnett’s post-hoc tests: RC vs EXT 10 p = 0.0938 RC vs EXT 30 **p = 0.0066, RC vs EXT 60 *p = 0.0251), e, When these tests were conducted with Adar1 shRNA-treated animals, Z-DNA was significantly increased (n = 4 animals per group from a single cohort ANOVA, F2,8 = 24.96 ***p<0.001, Dunnett’s post-hoc tests: RC SC vs EXT SC 10 p = 0.6690 RC SC vs EXT Adar1 ***p = 0.0007), f, Adar1 shRNA also blocked the significant increase in Adar1 binding (ANOVA, F2,15 = 9.798 **p<0.01, Dunnett’s post-hoc tests: RC SC vs EXT SC **p = 0.0027 RC SC vs EXT Adar1 p = 0.9897), g, Adar1 shRNA-treated animals had a significantly lower level of Nrxn3 transcript, (ANOVA, F2,10 = 3.345 p = 0.0772, Fisher’s LSD post-hoc tests: RC SC vs EXT SC p = 0.0956 RC SC vs EXT Adar1 *p = 0.0307).