SVA insertion in X-linked Dystonia Parkinsonism alters histone H3 acetylation associated with TAF1 gene

Tiziana Petrozziello, Amanda M. Dios, Kaly A. Mueller, Christine A. Vaine, William T. Hendriks, Kelly E. Glajch, Alexandra N. Mills, Kotchaphorn Mangkalaphiban, Ellen B. Penney, Naoto Ito, Cara Fernandez-Cerado, Gierold Paul A. Legarda, M. Salvie Velasco-Andrada, Patrick J. Acuña, Mark A. Ang, Edwin L. Muñoz, Cid Czarina E. Diesta, Regina Macalintal-Canlas, Geraldine Acuña, Nutan SharmaLaurie J. Ozelius, D. Cristopher Bragg, Ghazaleh Sadri-Vakili

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7 Scopus citations


X-linked Dystonia-Parkinsonism (XDP) is a neurodegenerative disease linked to an insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon within an intron of TAF1. This SVA insertion induces aberrant TAF1 splicing and partial intron retention, thereby decreasing levels of the full-length transcript. Here we sought to determine if these altered transcriptional dynamics caused by the SVA are also accompanied by local changes in histone acetylation, given that these modifications influence gene expression. Because TAF1 protein may itself exhibit histone acetyltransferase activity, we also examined whether decreased TAF1 expression in XDP cell lines and post-mortem brain affects global levels of acetylated histone H3 (AcH3). The results demonstrate that total AcH3 are not altered in XDP postmortem prefrontal cortex or cell lines. We also did not detect local differences in AcH3 associated with TAF1 exons or intronic sites flanking the SVA insertion. There was, however, a decrease in AcH3 association with the exon immediately proximal to the intronic SVA, and this decrease was normalized by CRISPR/Cas-excision of the SVA. Collectively, these data suggest that the SVA insertion alters histone status in this region, which may contribute to the dysregulation of TAF1 expression.

Original languageEnglish
Article numbere0243655
JournalPLoS ONE
Issue number12 December
StatePublished - Dec 2020
Externally publishedYes


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