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Dev Cell. 2012 Jan 17;22(1):38-51. doi: 10.1016/j.devcel.2011.11.013. Epub 2011 Dec 29.

DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy.

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1
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Abstract

Facioscapulohumeral dystrophy (FSHD) is one of the most common inherited muscular dystrophies. The causative gene remains controversial and the mechanism of pathophysiology unknown. Here we identify genes associated with germline and early stem cell development as targets of the DUX4 transcription factor, a leading candidate gene for FSHD. The genes regulated by DUX4 are reliably detected in FSHD muscle but not in controls, providing direct support for the model that misexpression of DUX4 is a causal factor for FSHD. Additionally, we show that DUX4 binds and activates LTR elements from a class of MaLR endogenous primate retrotransposons and suppresses the innate immune response to viral infection, at least in part through the activation of DEFB103, a human defensin that can inhibit muscle differentiation. These findings suggest specific mechanisms of FSHD pathology and identify candidate biomarkers for disease diagnosis and progression.

PMID:
22209328
PMCID:
PMC3264808
DOI:
10.1016/j.devcel.2011.11.013
[Indexed for MEDLINE]
Free PMC Article

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