Targeting H3K4 trimethylation in Huntington disease

Targeting H3K4 trimethylation in Huntington disease

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....

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Bibliographic Details
Main Authors: Ng, Christopher W., Yildirim, Ferah, Labadorf, Adam, Fraenkel, Ernest, Vashishtha, Malini, Kratter, Ian H., Bodai, Laszlo, Song, Wan, Lau, Alice L., Vogel-Ciernia, Annie, Troncosco, Juan, Ross, Christopher A., Bates, Gillian P., Krainc, Dimitri, Sadri-Vakili, Ghazaleh, Finkbeiner, Steven, Marsh, J. Lawrence, Thompson, Leslie M., Wasylenko, Theresa Anne, Housman, David E
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: National Academy of Sciences (U.S.) 2014
Online Access:http://hdl.handle.net/1721.1/85912
https://orcid.org/0000-0002-0524-5301
https://orcid.org/0000-0003-1381-4313
https://orcid.org/0000-0001-9249-8181
https://orcid.org/0000-0001-5016-0756
Description
Summary: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.

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