Targeting H3K4 trimethylation in Huntington disease.

Proc Natl Acad Sci U S A 2013 Aug 19;110(32):E3027-36. Epub 2013 Jul 19.

Department of Psychiatry and Human Behavior and UCI Institute of Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, USA.

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.

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http://dx.doi.org/10.1073/pnas.1311323110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740882PMC
August 2013
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References

(Supplied by CrossRef)

Cell 1993

Walker et al.
Lancet 2007

Cha et al.
Trends in neurosciences 2000

Cha et al.
Progress in neurobiology 2007

Zuccato et al.
Progress in neurobiology 2007

PNAS 2002

Santos-Rosa et al.
Nature; Physical Science (London) 2002

Kim et al.
Nature; Physical Science (London) 2005

PNAS 2009

Tsankova et al.
Nature neuroscience 2006

Jiang et al.
Journal of Neuroscience 2008

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