H3K27me3 Depletion during Differentiation Promotes Myogenic Transcription in Porcine Satellite Cells

H3K27me3 Depletion during Differentiation Promotes Myogenic Transcription in Porcine Satellite Cells
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分化过程中 H3K27me3 的缺失促进猪卫星细胞的生肌转录

DOI:
10.3390/genes10030231
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发表时间:
2019-03
期刊:
影响因子:
3.5
通讯作者:
Cao Jianhua
Cao Jianhua
中科院分区:
生物学3区
文献类型:
--
作者:
Wang Sheng;Sun Yan;Ren Ruimin;Xie Junhui;Tian Xiaohuan;Zhao Shuhong;Li Xinyun;Cao Jianhua

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背景:猪骨骼肌卫星细胞在肌肉发生和肌肉再生中起重要作用。转录组和组蛋白修饰的综合分析将揭示表观基因组在促进猪肌源性分化中的作用。方法:从新生仔猪中分离培养猪卫星细胞(PSCs)。利用增殖细胞和末端肌管进行RNA测序(RNA- seq)和染色质免疫沉淀测序(ChIP-Seq)实验,以查询转录组学特征,以及组蛋白标记h3k4me3、H3K27me3和h3k27ac和RNA聚合酶II的分布。结果:鉴定出917个细胞分化过程中的差异表达基因。表观遗传标记的景观是在全基因组尺度上展示的,这在全球范围内已经缩小。H3K27me3的增强参与阻碍增殖相关基因的转录,而其缺失则与肌源性基因的上调密切相关。此外,H3K27me3修饰程度显著降低50%,139个肌原性基因上调,促进细胞分化。结论:H3K27me3缺失可通过上调成肌基因的转录水平促进猪卫星细胞的分化。我们在这项研究中的发现为肌生成分化过程中发生的表观基因组机制提供了新的见解,并揭示了染色质状态和肌发生的动力学。
Background: Porcine skeletal muscle satellite cells play important roles in myogenesis and muscle regeneration. Integrated analysis of transcriptome and histone modifications would reveal epigenomic roles in promoting myogenic differentiation in swine. Methods: Porcine satellite cells (PSCs) were isolated and in-vitro cultured from newborn piglets. RNA Sequencing (RNA-Seq) and Chromatin Immunoprecipitation Sequencing (ChIP-Seq) experiments were performed using proliferating cells and terminal myotubes in order to interrogate the transcriptomic profiles, as well as the distribution of histone markers—H3K4me3, H3K27me3, and H3K27ac—and RNA polymerase II. Results: The study identified 917 differentially expressed genes during cell differentiation. The landscape of epigenetic marks was displayed on a genome-wide scale, which had globally shrunken. H3K27me3 reinforcement participated in obstructing the transcription of proliferation-related genes, while its depletion was closely related to the up-regulation of myogenic genes. Furthermore, the degree of H3K27me3 modification was dramatically reduced by 50%, and 139 myogenic genes were upregulated to promote cell differentiation. Conclusions: The depletion of H3K27me3 was shown to promote porcine satellite cell differentiation through upregulating the transcription level of myogenic genes. Our findings in this study provide new insights of the epigenomic mechanisms occurring during myogenic differentiation, and shed light on chromatin states and the dynamics underlying myogenesis.
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