Title |
Targeting H3K4 trimethylation in Huntington disease
|
---|---|
Published in |
Proceedings of the National Academy of Sciences of the United States of America, July 2013
|
DOI | 10.1073/pnas.1311323110 |
Pubmed ID | |
Authors |
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, Leslie M. Thompson |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 4 | 2% |
United States | 2 | 1% |
Portugal | 1 | <1% |
Austria | 1 | <1% |
Italy | 1 | <1% |
Japan | 1 | <1% |
Spain | 1 | <1% |
Unknown | 185 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 47 | 24% |
Researcher | 35 | 18% |
Student > Master | 24 | 12% |
Student > Bachelor | 20 | 10% |
Other | 10 | 5% |
Other | 22 | 11% |
Unknown | 38 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 52 | 27% |
Biochemistry, Genetics and Molecular Biology | 39 | 20% |
Neuroscience | 26 | 13% |
Medicine and Dentistry | 14 | 7% |
Chemistry | 6 | 3% |
Other | 16 | 8% |
Unknown | 43 | 22% |