Targeting H3K4 trimethylation in Huntington disease
Author(s)Ng, Christopher W.; Yildirim, Ferah; Gipson, Theresa Anne; Labadorf, Adam; Housman, David E.; 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.; ... Show more Show less
MetadataShow full item record
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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology
Proceedings of the National Academy of Sciences
National Academy of Sciences (U.S.)
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.
Final published version