A comprehensive epigenome atlas reveals DNA methylation regulating skeletal muscle development.
A comprehensive epigenome atlas reveals DNA methylation regulating skeletal muscle development.
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DOI：
10.1093/nar/gkaa1203
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发表时间：
2021-02-22
影响因子：
14.9
通讯作者：
Tang Z
中科院分区：
文献类型：
--
作者：
Yang Y;Fan X;Yan J;Chen M;Zhu M;Tang Y;Liu S;Tang Z
DNA甲基化对于基因表达的表观遗传调控是重要的，在哺乳动物的发育中起着关键作用。然而，骨骼肌发育过程中全基因组DNA甲基化的动态调节在很大程度上仍不清楚。在这里，我们制作了猪骨骼肌27个发育阶段的第一张单碱基分辨DNA甲基组和转录组图谱。从胚胎到成年，整个甲基化水平下降，这与DNMT1表达下调和部分甲基化结构域增加高度相关。值得注意的是，我们鉴定了超过40000个发育差异甲基化CPGS(DDMCs)，它们重建了骨骼肌的发育轨迹，并与肌肉发育基因和转录因子(TF)相关。DDMC在启动子调节区的表达明显不足，但作为增强子组蛋白标志物和染色质可及区强烈富含。综合分析显示，在骨骼肌发育过程中，与肌肉收缩和胰岛素信号相关的基因中，启动子和基因体甲基化都存在负调控。从机制上讲，DNA甲基化通过调节上游成肌因子结合的可达性来影响肌肉相关基因的表达，提示DNA甲基化/SP1/IGF2BP3轴参与了骨骼肌发生。我们的结果突出了动态DNA甲基化在骨骼肌发育中的作用和调节。
DNA methylation is important for the epigenetic regulation of gene expression and plays a critical role in mammalian development. However, the dynamic regulation of genome-wide DNA methylation in skeletal muscle development remains largely unknown. Here, we generated the first single-base resolution DNA methylome and transcriptome maps of porcine skeletal muscle across 27 developmental stages. The overall methylation level decreased from the embryo to the adult, which was highly correlated with the downregulated expression of DNMT1 and an increase in partially methylated domains. Notably, we identified over 40 000 developmentally differentially methylated CpGs (dDMCs) that reconstitute the developmental trajectory of skeletal muscle and associate with muscle developmental genes and transcription factors (TFs). The dDMCs were significantly under-represented in promoter regulatory regions but strongly enriched as enhancer histone markers and in chromatin-accessible regions. Integrative analysis revealed the negative regulation of both promoter and gene body methylation in genes associated with muscle contraction and insulin signaling during skeletal muscle development. Mechanistically, DNA methylation affected the expression of muscle-related genes by modulating the accessibly of upstream myogenesis TF binding, indicating the involvement of the DNA methylation/SP1/IGF2BP3 axis in skeletal myogenesis. Our results highlight the function and regulation of dynamic DNA methylation in skeletal muscle development.
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影响因子：
64.8
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
通讯作者：
Surani, M. Azim
DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.5
作者：
Gkountela S;Zhang KX;Shafiq TA;Liao WW;Hargan-Calvopiña J;Chen PY;Clark AT
通讯作者：
Clark AT
影响因子：
4.3
作者：
Laker RC;Ryall JG
通讯作者：
Ryall JG