Targeting H3K4 trimethylation in Huntington disease
Language: 
English
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.

Author(s): 
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: 
8/6/2013
Publication Year: 
2013
Pages: 
E3027-3036
Volume: 
110
Issue: 
32
ISSN: 
1091-6490
DOI: 
10.1073/pnas.1311323110
Library Catalog: 
PubMed
Extra: 
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>