Targeting H3K4 Trimethylation in Huntington Disease

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Jul 23

PMID 23872847

Citations 82

Authors

Malini Vashishtha

Christopher W Ng

Ferah Yildirim

Theresa A Gipson

Ian H Kratter

Laszlo Bodai

Wan Song

Alice Lau

Adam Labadorf

Annie Vogel-Ciernia

Juan Troncosco

Christopher A Ross

Gillian P Bates

Dimitri Krainc

Ghazaleh Sadri-Vakili

Steven Finkbeiner

J Lawrence Marsh

David E Housman

Ernest Fraenkel

Leslie M Thompson

Affiliations

Soon will be listed here.

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.

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