Small noncoding RNAs in FSHD2 muscle cells reveal both DUX4- and SMCHD1-specific signatures.
Small noncoding RNAs in FSHD2 muscle cells reveal both DUX4- and SMCHD1-specific signatures.
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FSHD2 肌肉细胞中的小非编码 RNA 揭示了 DUX4 和 SMCHD1 特异性特征。
DOI：
10.1093/hmg/ddy173
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发表时间：
2018
影响因子：
3.5
通讯作者：
Filippova,GalinaN
中科院分区：
文献类型：
--
作者：
Lim,Jong-Won;Wong,Chao-Jen;Yao,Zizhen;Tawil,Rabi;vanderMaarel,SilvèreM;Miller,DanielG;Tapscott,StephenJ;Filippova,GalinaN
面肩肱型肌营养不良症（FSHD）是由D4Z4大卫星重复序列的表观遗传抑制不足引起的，其中DUX4是FSHD致病基因。FSHD有两种形式，具有D4Z4重复序列收缩的FSHD 1和具有染色质致密缺陷的FSHD 2，主要是由于SMCHD1突变。先前的报道显示DUX4诱导的基因表达变化以及FSHD肌肉细胞中microRNA表达的变化。然而，小的非编码RNA，可能是由DUX4或SMCHD1突变调控的全基因组分析尚未报道。在这里，我们鉴定了几种类型的小的非编码RNA，包括已知的microRNA，与对照相比，它们在FSHD 2肌细胞中差异表达。尽管与对照相比，在FSHD 2细胞的肌肉分化过程中差异表达的小RNA较少，但大多数已知的肌源性microRNA，如miR1、miR133 a和miR206在FSHD 2和对照肌肉细胞中均在分化过程中被诱导。我们的小RNA测序数据分析还揭示了FSHD 2肌细胞中DUX4和SMCHD1特异性变化。对照成肌细胞中的六种FSHD 2 microRNA受到DUX 4过表达的影响，而FSHD 2肌细胞中tRNA和5S rRNA表达的增加在SMCHD 1缺失的对照成肌细胞中基本上得到了体现。总之，我们的研究表明，FSHD 2中的小非编码RNA转录组变化可能与FSHD 1中的变化不同，这些差异可能为FSHD 2提供新的诊断和治疗工具。
Facioscapulohumeral muscular dystrophy (FSHD) is caused by insufficient epigenetic repression of D4Z4 macrosatellite repeat where DUX4, an FSHD causing gene is embedded. There are two forms of FSHD, FSHD1 with contraction of D4Z4 repeat and FSHD2 with chromatin compaction defects mostly due to SMCHD1 mutation. Previous reports showed DUX4-induced gene expression changes as well as changes in microRNA expression in FSHD muscle cells. However, a genome wide analysis of small noncoding RNAs that might be regulated by DUX4 or by mutations in SMCHD1 has not been reported yet. Here, we identified several types of small noncoding RNAs including known microRNAs that are differentially expressed in FSHD2 muscle cells compared to control. Although fewer small RNAs were differentially expressed during muscle differentiation in FSHD2 cells compared to controls, most of the known myogenic microRNAs, such as miR1, miR133a and miR206 were induced in both FSHD2 and control muscle cells during differentiation. Our small RNA sequencing data analysis also revealed both DUX4- and SMCHD1-specific changes in FSHD2 muscle cells. Six FSHD2 microRNAs were affected by DUX4 overexpression in control myoblasts, whereas increased expression of tRNAs and 5S rRNAs in FSHD2 muscle cells was largely recapitulated in SMCHD1-depleted control myoblasts. Altogether, our studies suggest that the small noncoding RNA transcriptome changes in FSHD2 might be different from those in FSHD1 and that these differences may provide new diagnostic and therapeutic tools specific to FSHD2.
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