Figure 1. Screen to identify SpCas9 gRNAs that unsilence paternal Ube3a.
a. Paternal Ube3a-ATS locus showing the location of genes, transcription collision region (dashed lines), and gRNA library target sites.
b. Percentage of Ube3am+/pYFP neurons co-stained for UBE3A-YFP and tdTomato; co-transfected with CamKIIα promoter:tdTomato, SpCas9 and one gRNA (circles) or treated with 300 nM topotecan for 72 h. Black circles, P<0.005 and fold change >4.
c. Ube3am+/pYFP neurons co-transfected with CamKIIα promoter:tdTomato, SpCas9 and negative control gRNA (neg.) or Spjw33 gRNA. Nuclei, blue (DAPI). Scale bar, 100 μm.
d. Expression of the indicated genes seven days after transducing Ube3am+/pYFP cortical neurons with lentiviral SpCas9+Spjw33, relative to SpCas9+neg. control gRNA (dashed line). qPCR, normalized to Eif4a2, n=3. Error bars, standard error of the mean (S.E.M.), * P<0.01.