Proceedings of the National Academy of Sciences - PNAS, 2013-08, Vol.110 (32), p.E3027-E3036
- 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
2013
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- Autor(en) / Beteiligte
- 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
- Titel
- Targeting H3K4 trimethylation in Huntington disease
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2013-08, Vol.110 (32), p.E3027-E3036
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1311323110Titel-ID: cdi_pubmed_primary_23872847
- Format
- –
- Schlagworte
- Amino acids, Animals, Animals, Genetically Modified, Biological Sciences, Blotting, Western, Brain - metabolism, Brain - pathology, Brain-Derived Neurotrophic Factor - genetics, Brain-Derived Neurotrophic Factor - metabolism, Cells, Cultured, Drosophila melanogaster - genetics, Drosophila melanogaster - metabolism, Epigenetics, Female, Gene expression, Gene Expression Profiling, Histones - metabolism, Humans, Huntingtin Protein, Huntington Disease - genetics, Huntington Disease - metabolism, Huntingtons disease, Insects, Lysine - metabolism, Male, Methylation, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Neurons - cytology, Neurons - metabolism, Oxidoreductases, N-Demethylating - genetics, Oxidoreductases, N-Demethylating - metabolism, PNAS Plus, Promoter Regions, Genetic - genetics, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference