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分化过程中 H3K27me3 的耗竭促进猪卫星细胞的成肌转录。

H3K27me3 Depletion during Differentiation Promotes Myogenic Transcription in Porcine Satellite Cells.

机构信息

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China.

The Cooperative Innovation Center for Sustainable Pig Production-Swine Breeding and Reproduction Innovation Platform, Huazhong Agricultural University, Wuhan 430070, China.

出版信息

Genes (Basel). 2019 Mar 19;10(3):231. doi: 10.3390/genes10030231.

Abstract

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.

摘要

背景

猪骨骼肌卫星细胞在肌发生和肌肉再生中发挥重要作用。对转录组和组蛋白修饰进行综合分析,将揭示其在促进猪肌肉发生分化中的表观遗传作用。

方法

从新生仔猪中分离和体外培养猪卫星细胞(PSCs)。进行 RNA 测序(RNA-Seq)和染色质免疫沉淀测序(ChIP-Seq)实验,以研究增殖细胞和终末肌管中的转录组谱,以及组蛋白标记 H3K4me3、H3K27me3 和 H3K27ac 的分布和 RNA 聚合酶 II。

结果

该研究在细胞分化过程中鉴定出 917 个差异表达基因。在全基因组范围内显示了表观遗传标记的图谱,该图谱整体缩小。H3K27me3 强化参与阻止增殖相关基因的转录,而其耗竭与肌生成基因的上调密切相关。此外,H3K27me3 修饰程度显著降低了 50%,有 139 个肌生成基因上调以促进细胞分化。

结论

H3K27me3 的耗竭通过上调肌生成基因的转录水平,促进猪卫星细胞分化。本研究中的发现为肌发生分化过程中的表观遗传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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e616/6471710/2f96745b8bf9/genes-10-00231-g001.jpg

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