Nucleus Type-Specific DNA Methylomics Reveals Epigenetic "Memory" of Prior Adaptation in Skeletal Muscle.
Nucleus Type-Specific DNA Methylomics Reveals Epigenetic "Memory" of Prior Adaptation in Skeletal Muscle.
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DOI：
10.1093/function/zqab038
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Murach KA
中科院分区：
文献类型：
--
作者：
Wen Y;Dungan CM;Mobley CB;Valentino T;von Walden F;Murach KA
使用小鼠模型的条件和诱导的体内荧光标记（HSA-GFP），分选纯化的细胞核，低输入减少代表性亚硫酸氢盐测序（RRBS），和一个可翻译的和可逆的运动模型（渐进加权轮运行，PoWeR），我们提供了第一个核类型特异性表观遗传信息骨骼肌适应和停止训练。成年（>4个月）HSA-GFP小鼠进行PoWeR 8周，然后停止训练12周;年龄匹配的未经训练的小鼠用于对照研究的长持续时间。分离跖肌的肌核和间质核用于RRBS。相对于未经训练的，PoWeR引起类似的myocardial CpG启动子区域的低甲基化和高甲基化，以及间质核启动子的大量低甲基化。启动子的过度代表性分析显示，在训练后的两个核群中有大量的高甲基化途径与低甲基化途径，并且有证据表明核类型之间的甲基化相互调节，肌核中Wnt信号相关基因的启动子区域低甲基化和间质核中的高甲基化。停训12周后，记录的肌肉重塑相关基因和途径中的启动子CpG在PoWeR后立即差异甲基化，在肌核中持续差异甲基化，沿着间质核中的长期启动子低甲基化。使用RNA测序没有观察到肌肉组织中持久的基因表达变化。经过4周的再训练，先前训练过的小鼠在整个肌肉和纤维类型特异性细胞水平上比训练过的小鼠生长得更多，肌细胞数量没有差异。肌肉细胞核具有先前训练的甲基化表观记忆，可以增强肌肉对再训练的适应性。
Using a mouse model of conditional and inducible in vivo fluorescent myonuclear labeling (HSA-GFP), sorting purification of nuclei, low-input reduced representation bisulfite sequencing (RRBS), and a translatable and reversible model of exercise (progressive weighted wheel running, PoWeR), we provide the first nucleus type-specific epigenetic information on skeletal muscle adaptation and detraining. Adult (>4 mo) HSA-GFP mice performed PoWeR for 8 wk then detrained for 12 wk; age-matched untrained mice were used to control for the long duration of the study. Myonuclei and interstitial nuclei from plantaris muscles were isolated for RRBS. Relative to untrained, PoWeR caused similar myonuclear CpG hypo- and hyper-methylation of promoter regions and substantial hypomethylation in interstitial nuclear promoters. Over-representation analysis of promoters revealed a larger number of hyper- versus hypo-methylated pathways in both nuclear populations after training and evidence for reciprocal regulation of methylation between nucleus types, with hypomethylation of promoter regions in Wnt signaling-related genes in myonuclei and hypermethylation in interstitial nuclei. After 12 wk of detraining, promoter CpGs in documented muscle remodeling-associated genes and pathways that were differentially methylated immediately after PoWeR were persistently differentially methylated in myonuclei, along with long-term promoter hypomethylation in interstitial nuclei. No enduring gene expression changes in muscle tissue were observed using RNA-sequencing. Upon 4 wk of retraining, mice that trained previously grew more at the whole muscle and fiber type-specific cellular level than training naïve mice, with no difference in myonuclear number. Muscle nuclei have a methylation epi-memory of prior training that may augment muscle adaptability to retraining.
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影响因子：
4
作者：
Guzzoni V;Ribeiro MBT;Lopes GN;de Cássia Marqueti R;de Andrade RV;Selistre-de-Araujo HS;Durigan JLQ
通讯作者：
Durigan JLQ
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通讯作者：
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影响因子：
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作者：
Grozdanov, P;Georgiev, O;Karagyozov, L
通讯作者：
Karagyozov, L