DUX4-induced gene expression is the major molecular signature in FSHD skeletal muscle.
DUX4-induced gene expression is the major molecular signature in FSHD skeletal muscle.
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DUX4 诱导的基因表达是 FSHD 骨骼肌的主要分子特征。
DOI：
10.1093/hmg/ddu251
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发表时间：
2014
影响因子：
3.5
通讯作者：
Tapscott,StephenJ
中科院分区：
文献类型：
--
作者：
Yao,Zizhen;Snider,Lauren;Balog,Judit;Lemmers,RichardJLF;VanDerMaarel,SilvèreM;Tawil,Rabi;Tapscott,StephenJ
FSHD是由D4Z4大卫星阵列的表观遗传抑制减少引起的，最近的研究表明，这导致了DUX4在骨骼肌中的低水平表达。FSHD的病理生理学机制还有其他几种，目前尚不清楚DUX4的表达是否可以解释FSHD的大部分分子变化。由于DUX4是一种转录因子，我们使用RNA-seq技术检测了转导DUX4的肌肉细胞以及对照组和FSHD患者的肌肉细胞和活检组织中的基因表达。我们发现，DUX4靶基因的表达是FSHD肌肉的主要分子特征，同时也是免疫细胞渗透的基因表达特征。此外，一名未受影响的个体没有已知的导致FSHD的突变，显示出DUX4靶基因的表达。这个人有一个患有FSHD的兄弟姐妹，也没有已知的导致FSHD的突变，这表明存在一个未知的DUX4表达和FSHD的修饰基因。这些发现表明，DUX4的表达是FSHD骨骼肌基因表达变化的主要原因，同时还有免疫细胞的渗透。
Facioscapulohumeral dystrophy (FSHD) is caused by decreased epigenetic repression of the D4Z4 macrosatellite array and recent studies have shown that this results in the expression of low levels of the DUX4 mRNA in skeletal muscle. Several other mechanisms have been suggested for FSHD pathophysiology and it remains unknown whether DUX4 expression can account for most of the molecular changes seen in FSHD. Since DUX4 is a transcription factor, we used RNA-seq to measure gene expression in muscle cells transduced with DUX4, and in muscle cells and biopsies from control and FSHD individuals. We show that DUX4 target gene expression is the major molecular signature in FSHD muscle together with a gene expression signature consistent with an immune cell infiltration. In addition, one unaffected individual without a known FSHD-causing mutation showed the expression of DUX4 target genes. This individual has a sibling with FSHD and also without a known FSHD-causing mutation, suggesting the presence of an unidentified modifier locus for DUX4 expression and FSHD. These findings demonstrate that the expression of DUX4 accounts for the majority of the gene expression changes in FSHD skeletal muscle together with an immune cell infiltration.
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影响因子：
64.8
作者：
Gabellini, D;D'Antona, G;Tupler, R
通讯作者：
Tupler, R
影响因子：
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作者：
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通讯作者：
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作者：
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影响因子：
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作者：
S. Friedman;S. Poliachik;Randolph K. Otto;G. Carter;C. Budech;T. Bird;Daniel G. Miller;D. Shaw
通讯作者：
D. Shaw
影响因子：
11.8
作者：
Geng, Linda N.;Yao, Zizhen;Snider, Lauren;Fong, Abraham P.;Cech, Jennifer N.;Young, Janet M.;van der Maarel, Silvere M.;Ruzzo, Walter L.;Gentleman, Robert C.;Tawil, Rabi;Tapscott, Stephen J.
通讯作者：
Tapscott, Stephen J.