DUX4 promotes transcription of FRG2 by directly activating its promoter in facioscapulohumeral muscular dystrophy

Skeletal Muscle
Peter E ThijssenSilvère M van der Maarel

Abstract

The most common form of facioscapulohumeral muscular dystrophy (FSHD) is caused by a genetic contraction of the polymorphic D4Z4 macrosatellite repeat array in the subtelomeric region of chromosome 4q. In some studies, genes centromeric to the D4Z4 repeat array have been reported to be over-expressed in FSHD, including FRG1 and FRG2, presumably due to decreased long-distance repression by the shorter array through a mechanism similar to position-effect variegation. Differential regulation of FRG1 in FSHD has never been unequivocally proven, however, FRG2 has been reproducibly shown to be induced in primary FSHD-derived muscle cells when differentiated in vitro. The molecular function of FRG2 and a possible contribution to FSHD pathology remain unclear. Recent evidence has identified the mis-expression of DUX4, located within the D4Z4 repeat unit, in skeletal muscle as the cause of FSHD. DUX4 is a double homeobox transcription factor that has been shown to be toxic when expressed in muscle cells. We used a combination of expression analysis by qRT/PCR and RNA sequencing to determine the transcriptional activation of FRG2 and DUX4. We examined this in both differentiating control and FSHD derived muscle cell cultures or DUX4 tran...Continue Reading

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Citations

Jan 30, 2016·Skeletal Muscle·Yu ZhangMichael Kyba
Jul 29, 2015·Journal of Cellular Physiology·Carla DibYegor S Vassetzky
Jan 26, 2020·International Journal of Molecular Sciences·Kenji Rowel Q LimToshifumi Yokota
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Jun 22, 2021·EMBO Molecular Medicine·Christopher R S Banerji, Peter S Zammit
Sep 25, 2021·Human Molecular Genetics·Richard J L F LemmersSilvère M van der Maarel

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Datasets Mentioned

BETA
GSE33838

Methods Mentioned

BETA
biopsies
transgenic
FCS
PCR
transfection
ChIP
RNA-seq
ChIP-seq
immunoprecipitation

Software Mentioned

UCSC genome browser
IGV genome viewer

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