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. 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.

Vashishtha, Malini
Ng, Christopher W.
Yildirim, Ferah
Gipson, Theresa A.
Kratter, Ian H.
Bodai, Laszlo
Song, Wan
Lau, Alice
Labadorf, Adam
Vogel-Ciernia, Annie
Troncosco, Juan
Ross, Christopher A.
Bates, Gillian P.
Krainc, Dimitri
Sadri-Vakili, Ghazaleh
Finkbeiner, Steven
Marsh, J. Lawrence
Housman, David E.
Fraenkel, Ernest
Thompson, Leslie M.
Item Type: 
Journal Article
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America
Journal Abbreviation: 
Proc. Natl. Acad. Sci. U.S.A.
Publication Date: 
Publication Year: 
Library Catalog: 
PMID: 23872847 PMCID: PMC3740882

Turabian/Chicago Citation

Malini Vashishtha, Christopher W. Ng, Ferah Yildirim, Theresa A. Gipson, Ian H. Kratter, Laszlo Bodai, Wan Song, Alice Lau, Adam Labadorf, Annie Vogel-Ciernia, Juan Troncosco, Christopher A. Ross, Gillian P. Bates, Dimitri Krainc, Ghazaleh Sadri-Vakili, Steven Finkbeiner, J. Lawrence Marsh, David E. Housman, Ernest Fraenkel and Leslie M. Thompson. 8/6/2013. "Targeting H3K4 trimethylation in Huntington disease." Proceedings of the National Academy of Sciences of the United States of America 110: 32: E3027-3036. 10.1073/pnas.1311323110.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1073/pnas.1311323110 | issn = 1091-6490 | volume = 110 | pages = E3027-3036 | last = Vashishtha | first = Malini | coauthors = Ng, Christopher W., Yildirim, Ferah, Gipson, Theresa A., Kratter, Ian H., Bodai, Laszlo, Song, Wan, Lau, Alice, Labadorf, Adam, Vogel-Ciernia, Annie, Troncosco, Juan, Ross, Christopher A., Bates, Gillian P., Krainc, Dimitri, Sadri-Vakili, Ghazaleh, Finkbeiner, Steven, Marsh, J. Lawrence, Housman, David E., Fraenkel, Ernest, Thompson, Leslie M. | title = Targeting H3K4 trimethylation in Huntington disease | journal = Proceedings of the National Academy of Sciences of the United States of America | date = 8/6/2013 | pmid = | pmc = }} </ref>