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....
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2014
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| 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 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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 |
| author_sort | Ng, Christopher W. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:32:38Z |
| format | Article |
| id | mit-1721.1/85912 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:32:38Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/859122022-09-23T12:48:04Z Targeting H3K4 trimethylation in Huntington disease 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 Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Ng, Christopher W. Yildirim, Ferah Gipson, Theresa Anne Labadorf, Adam Housman, David E. Fraenkel, Ernest 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. National Institutes of Health (U.S.) (Grant U54-CA112967) National Institutes of Health (U.S.) (Grant R01-GM089903) National Institutes of Health (U.S.) (Grant PN2EY016525) Hereditary Disease Foundation (U.S.) (Leslie Gehry Brenner Award for Innovation in Science) National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051) 2014-03-24T18:35:41Z 2014-03-24T18:35:41Z 2013-08 2013-05 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/85912 Vashishtha, M., C. W. Ng, F. Yildirim, T. A. Gipson, I. H. Kratter, L. Bodai, W. Song, et al. “Targeting H3K4 Trimethylation in Huntington Disease.” Proceedings of the National Academy of Sciences 110, no. 32 (August 6, 2013): E3027–E3036. 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 en_US http://dx.doi.org/10.1073/pnas.1311323110 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Science (U.S.) |
| spellingShingle | 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 Targeting H3K4 trimethylation in Huntington disease |
| title | Targeting H3K4 trimethylation in Huntington disease |
| title_full | Targeting H3K4 trimethylation in Huntington disease |
| title_fullStr | Targeting H3K4 trimethylation in Huntington disease |
| title_full_unstemmed | Targeting H3K4 trimethylation in Huntington disease |
| title_short | Targeting H3K4 trimethylation in Huntington disease |
| title_sort | targeting h3k4 trimethylation in huntington disease |
| url | 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 |
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