Targeting H3K4 trimethylation in Huntington disease
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Vashishtha-2013-Targeting H3K4 trime.pdf
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1.31 MB
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Author(s)
Ng, Christopher W.
Yildirim, Ferah
Labadorf, Adam
Fraenkel, Ernest
Vashishtha, Malini
Kratter, Ian H.
Bodai, Laszlo
Song, Wan
Lau, Alice L.
Vogel-Ciernia, Annie
Date Issued
August 2013
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1311323110
