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- Malini Vashishtha
- Department of Psychiatry and Human Behavior and UCI Institute of Memory Impairments and Neurological Disorders,
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- Christopher W. Ng
- Department of Biological Engineering and
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- Ferah Yildirim
- Department of Biological Engineering and
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- Theresa A. Gipson
- Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
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- Ian H. Kratter
- Gladstone Institute of Neurological Disease Biomedical Sciences Graduate Program and Medical Scientist Training Program and
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- Laszlo Bodai
- Department of Developmental and Cell Biology and Developmental Biology Center, and
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- Wan Song
- Department of Developmental and Cell Biology and Developmental Biology Center, and
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- Alice Lau
- Department of Psychiatry and Human Behavior and UCI Institute of Memory Impairments and Neurological Disorders,
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- Adam Labadorf
- Department of Biological Engineering and
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- Annie Vogel-Ciernia
- Department of Neurobiology and Behavior, University of California, Irvine, CA 92697;
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- Juan Troncosco
- Departments of Psychiatry, Neurology, and Neuroscience and Neuropathology, Johns Hopkins University, Baltimore, MD 21287;
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- Christopher A. Ross
- Departments of Psychiatry, Neurology, and Neuroscience and Neuropathology, Johns Hopkins University, Baltimore, MD 21287;
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- Gillian P. Bates
- Department of Medical and Molecular Genetics, King's College, London SE1 9RT, United Kingdom; and
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- Dimitri Krainc
- Department of Neurology, Massachusetts General Hospital, Boston, MA 02114
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- Ghazaleh Sadri-Vakili
- Department of Neurology, Massachusetts General Hospital, Boston, MA 02114
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- Steven Finkbeiner
- Gladstone Institute of Neurological Disease Taube-Koret Center for Huntington’s Disease Research, Departments of Neurology and Physiology, University of California, San Francisco, CA 94158;
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- J. Lawrence Marsh
- Department of Developmental and Cell Biology and Developmental Biology Center, and
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- David E. Housman
- Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
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- Ernest Fraenkel
- Department of Biological Engineering and
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- Leslie M. Thompson
- Department of Psychiatry and Human Behavior and UCI Institute of Memory Impairments and Neurological Disorders,
説明
<jats:title>Significance</jats:title> <jats:p> Transcriptional dysregulation is an early and reproducible feature of Huntington disease (HD); however, mechanisms underlying this dysregulation are unclear. This article describes a unique pattern of the chromatin mark H3K4me3 at transcriptionally repressed promoters in HD mouse and human brain identified by genome-wide analysis. Reducing the levels of the demethylase <jats:italic>SMCX/Jarid1c</jats:italic> in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression and was neuroprotective in a <jats:italic>Drosophila</jats:italic> HD model. These results suggest that targeting epigenetic signatures may be an effective strategy to ameliorate the consequences of HD and other neurodegenerative diseases. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 110 (32), E3027-, 2013-07-19
Proceedings of the National Academy of Sciences