Targeting H3K4 trimethylation in Huntington disease.
basic_science · Level V
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- Record sourced from PubMed, PMID 23872847.
- Also identified by DOI 10.1073/pnas.1311323110 and PMC identifier 3740882.
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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.
Medical subject headings
- Brain
- Histones
- Huntington Disease
- Lysine