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Targeting H3K4 trimethylation in Huntington disease PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Vashishtha, M., Ng, C. W., Yildirim, F., Gipson, T. A., Kratter, I. H., Bodai, L., Song, W., Lau, A., Labadorf, A., Vogel-Ciernia, A., Troncosco, J., Ross, C. A., Bates, G. P., Krainc, D., Sadri-Vakili, G., Finkbeiner, S., Marsh, J., Housman, D. E., Fraenkel, E., Thompson, L. M. 2013; 110 (32): E3027–E3036

Abstract

Transcriptional dysregulation is an early feature of Huntington disease (HD). We observed gene-specific changes in histone H3 lysine 4 trimethylation (H3K4me3) at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD.

View details for DOI 10.1073/pnas.1311323110

View details for Web of Science ID 000322771100015

View details for PubMedID 23872847

View details for PubMedCentralID PMC3740882