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Huntington's disease (HD)

Jumonji/ARID domain containing protein 1C (KDM5C; JARID1C)

Studies in patient samples, cultured cells and flies suggest inhibiting JARID1C could help to treat HD. In brain tissue from HD patients, trimethylation of histone H3 at lysine 4 (H3K4) was decreased on genes that were expressed at lower levels compared with tissues from healthy individuals. In cultured mouse neurons expressing mutant Huntingtin (Htt), shRNA knockdown of the H3K4 demethylase−encoding Kdm5c increased the expression of these target genes compared with control shRNA. In a fly model of HD, insects lacking one copy of a gene encoding an H3K4 demethylase had a less severe disease phenotype compared with flies carrying both copies of the gene. Next steps could include identifying downstream genes regulated by JARID1C that contribute to HD pathology.

SciBX 6(31); doi:10.1038/scibx.2013.830
Published online Aug. 15, 2013

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Vashishtha, M. et al. Proc. Natl. Acad. Sci. USA; published online
July 19, 2013;
Contact: Leslie M. Thompson, University of California, Irvine, Calif.
Contact: Ernest Fraenkel, Massachusetts Institute of Technology, Cambridge, Mass.
Contact: David E. Housman, same affiliation as above