Targeting H3K4 trimethylation in Huntington disease

Author(s)
Ng, Christopher W.; Yildirim, Ferah; Labadorf, Adam; Fraenkel, Ernest; Vashishtha, Malini; ... Show more
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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.
Date issued
2013-08
URI
http://hdl.handle.net/1721.1/85912
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MIT
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Vashishtha, M., C. W. Ng, F. Yildirim, T. A. Gipson, I. H. Kratter, L. Bodai, W. Song, et al. “Targeting H3K4 Trimethylation in Huntington Disease.” Proceedings of the National Academy of Sciences 110, no. 32 (August 6, 2013): E3027–E3036.
Version: Final published version
ISSN
0027-8424
1091-6490
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