Transcriptomic analysis of ZNF91 knockout in XDP iPSCs

X-linked Dystonia-Parkinsonism (XDP) is a severe neurodegenerative disorder resulting from the insertion of an intronic SINE-Alu-VNTR (SVA) retrotransposon in the TAF1 gene. Recent research has revealed that the pathogenic XDP-SVA insertion leads to dysregulation of TAF1 transcription, including increased intron retention and decreased expression of exons surrounding the insertion. The Kruppel-associated box (KRAB) zinc finger protein, ZNF91, is a critical repressor of SVA retrotransposons. However, the functional consequences of ZNF91 repression of the XDP-SVA on the associated molecular phenotype remain unclear. In this study, we used CRISPR/Cas9 to genetically delete ZNF91 from induced pluripotent stem cell (iPSC) lines derived from XDP patients and isogenic controls lacking the XDP-SVA insertion (dSVA). Total RNA-seq was used to validate ZNF91 knockout and capture RNA-sequencing (cap-seq) used to assess TAF1 transcription changes.