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肥胖兔骨骼肌中 DNA 甲基化和基因可变剪接的分子谱分析。

Molecular Profiling of DNA Methylation and Alternative Splicing of Genes in Skeletal Muscle of Obese Rabbits.

机构信息

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

Department of Animal Sciences, University of Florida, Gainesville, FL 32611, USA.

出版信息

Curr Issues Mol Biol. 2021 Oct 11;43(3):1558-1575. doi: 10.3390/cimb43030110.

DOI:10.3390/cimb43030110
PMID:34698087
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8929151/
Abstract

DNA methylation and the alternative splicing of precursor messenger RNAs (pre-mRNAs) are two important genetic modification mechanisms. However, both are currently uncharacterized in the muscle metabolism of rabbits. Thus, we constructed the Tianfu black rabbit obesity model (obese rabbits fed with a 10% high-fat diet and control rabbits from 35 days to 70 days) and collected the skeletal muscle samples from the two groups for Genome methylation sequencing and RNA sequencing. DNA methylation data showed that the promoter regions of 599 genes and gene body region of 2522 genes had significantly differential methylation rates between the two groups, of which 288 genes had differential methylation rates in promoter and gene body regions. Analysis of alternative splicing showed 555 genes involved in exon skipping (ES) patterns, and 15 genes existed in differential methylation regions. Network analysis showed that 20 hub genes were associated with ubiquitinated protein degradation, muscle development pathways, and skeletal muscle energy metabolism. Our findings suggest that the two types of genetic modification have potential regulatory effects on skeletal muscle development and provide a basis for further mechanistic studies in the rabbit.

摘要

DNA 甲基化和前体信使 RNA(pre-mRNAs)的选择性剪接是两种重要的遗传修饰机制。然而,目前在兔肌肉代谢中这两种机制均未被描述。因此,我们构建了天府黑兔肥胖模型(肥胖兔喂食 10%高脂肪饮食,对照组兔从 35 天到 70 天),并从两组中采集骨骼肌样本进行基因组甲基化测序和 RNA 测序。DNA 甲基化数据分析显示,两组之间有 599 个基因的启动子区域和 2522 个基因的基因体区域的甲基化率存在显著差异,其中 288 个基因在启动子和基因体区域的甲基化率存在差异。选择性剪接分析显示,有 555 个基因存在外显子跳跃(ES)模式,并且在差异甲基化区域中存在 15 个基因。网络分析显示,有 20 个枢纽基因与泛素化蛋白降解、肌肉发育途径和骨骼肌能量代谢有关。我们的研究结果表明,这两种遗传修饰类型对骨骼肌发育可能具有潜在的调节作用,并为兔的进一步机制研究提供了基础。

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