数字农科院2.0

Identification of Robust and Key Differentially Expressed Genes during C2C12 Cell Myogenesis Based on Multiomics Data

文献类型： 外文期刊

作者： Zhang, Song;Zhang, Yuanyuan;Chen, Choulin;Hu, Qingqing;Fu, Yang;Xu, Lingna;Wang, Chao;Liu, Yuwen

作者机构：

关键词： myogenesis;differentially expressed genes;robust rank aggregation;KLF5;enhancer

期刊名称： INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ISSN：

年卷期： 2022 年 23 卷 11 期

页码：

摘要： Myogenesis is a central step in prenatal myofiber formation, postnatal myofiber hypertrophy, and muscle damage repair in adulthood. RNA-Seq technology has greatly helped reveal the molecular mechanism of myogenesis, but batch effects in different experiments inevitably lead to misinterpretation of differentially expressed genes (DEGs). We previously applied the robust rank aggregation (RRA) method to effectively circumvent batch effects across multiple RNA-Seq datasets from 3T3-L1 cells. Here, we also used the RRA method to integrate nine RNA-Seq datasets from C2C12 cells and obtained 3140 robust DEGs between myoblasts and myotubes, which were then validated with array expression profiles and H3K27ac signals. The upregulated robust DEGs were highly enriched in gene ontology (GO) terms related to muscle cell differentiation and development. Considering that the cooperative binding of transcription factors (TFs) to enhancers to regulate downstream gene expression is a classical epigenetic mechanism, differentially expressed TFs (DETFs) were screened, and potential novel myogenic factors (MAF, BCL6, and ESR1) with high connection degree in protein-protein interaction (PPI) network were presented. Moreover, KLF5 cooperatively binds with the three key myogenic factors (MYOD, MYOG, and MEF2D) in C2C12 cells. Motif analysis speculates that the binding of MYOD and MYOG is KLF5-independent, while MEF2D is KLF5-dependent. It was revealed that KLF5-binding sites could be exploited to filter redundant MYOD-, MYOG-, and MEF2D-binding sites to focus on key enhancers for myogenesis. Further functional annotation of KLF5-binding sites suggested that KLF5 may regulate myogenesis through the PI3K-AKt signaling pathway, Rap1 signaling pathway, and the Hippo signaling pathway. In general, our study provides a wealth of untapped candidate targets for myogenesis and contributes new insights into the core regulatory mechanisms of myogenesis relying on KLF5-binding signal.

分类号：

  • 相关文献

[1]Identification and characterization of GHR gene promoter of yak. Wu, Xiaoyun,Chu, Min,Shi, Yilin,Wang, Fubin,Ma, Xiaoming,Ge, Qianyun,Guo, Xian,Liang, Chunnian,Yan, Ping. 2025

[2]Functional analysis of helicase gene promoter and homologous region 3 enhancer in Bombyx mori nuclear polyhedrosis virus. Xiao, QL,Zhang, ZF,Yi, YZ,He, JL,Wu, XF. 2001

[3]Homologous region 3 from Bombyx mori nucleopolyhedrovirus enhancing the transcriptional activity of heat shock cognate 70-4 promoter from Bombyx mori and Bombyx mandarina in vitro and in vivo. Tang, SM,Zhao, QL,Yi, YZ,Zhang, ZF,Li, YR. 2005

[4]A constitutive super-enhancer: homologous region 3 of Bombyx mori nucleopolyhedrovirus. Chen, Y,Yao, B,Zhu, ZZ,Yi, YZ,Lin, X,Zhang, ZF,Shen, GF. 2004

[5]A review of enhancers for chemiluminescence enzyme immunoassay. Chen, Ge,Jin, Maojun,Du, Pengfei,Zhang, Chan,Cui, Xueyan,Zhang, Yudan,Wang, Jing,Jin, Fen,She, Yongxin,Shao, Hua,Wang, Shanshan,Zheng, Lufei.

[6]PorcineAI-Enhancer: Prediction of Pig Enhancer Sequences Using Convolutional Neural Networks. Ji Wang,Han Zhang,Nanzhu Chen,Tong Zeng,Xiaohua Ai,Keliang Wu. 2023

[7]Targeted insertion of regulatory elements enables translational enhancement in rice. Rundong Shen,Qi Yao,Dating Zhong,Xuening Zhang,Xinbo Li,Xuesong Cao,Chao Dong,Yifu Tian,Jian Kang Zhu,Yuming Lu. 2023

[8]A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1. Xiao Yan Wang,Zixuan Chen,Eduard Murani,Enrico D’Alessandro,Yalong An,Cai Chen,Kui Li,Grazia Galeano,Klaus Wimmers,Chengyi Song. 2021

[9]DEtail-seq is an ultra-efficient and convenient method for meiotic DNA break profiling in multiple organisms. Xu, Wei,Liu, Chao,Zhang, Zhe,Sun, Changbin,Li, Qin,Li, Kuan,Jiang, Hui,Li, Wei,Sun, Qianwen. 2023

[10]Regulatory element map of sheep reproductive tissues: functional annotation of tissue-specific strong active enhancers. Meng, Zhu,Chu, Mingxing,Yang, Hao,Zhang, Shiwen,Wang, Qiangjun,Chen, Jiahong,Ren, Chunhuan,Pan, Zhangyuan,Zhang, Zijun. 2025

[11]The effect of myostatin silencing by lentiviral-mediated RNA interference on goat fetal fibroblasts. Lu, Jian,Wei, Caihong,Zhang, Xiaoning,Xu, Lingyang,Zhang, Shifang,Liu, Jiasen,Cao, Jiaxue,Zhao, Fuping,Zhang, Li,Du, Lixin,Lu, Jian,Lu, Jian,Li, Bichun,Liu, Jiasen,Cao, Jiaxue.

[12]Identification of Histone Deacetylase 2 as a Functional Gene for Skeletal Muscle Development in Chickens. Shahjahan, Md.,Wang, Fangjie,Liu, Ranran,Zhao, Guiping,Zheng, Maiqing,Zhang, Jingjing,Song, Jiao,Wen, Jie.

[13]Conservative analysis of Synaptopodin-2 intron sense-overlapping lncRNA reveals its novel function in promoting muscle atrophy. Jin, Jianjun,Du, Mengmeng,Wang, Jian,Guo, Yubo,Zhang, Jiali,Zuo, Hao,Hou, Yunqing,Wang, Shanshan,Lv, Wei,Bai, Wei,Wang, Jin,Zhan, Xizhen,Peng, Yaxin,Tong, Qian,Chai, Jin,Xu, Zaiyan,Zuo, Bo. 2022

[14]A newly identified lncRNA lnc000100 regulates proliferation and differentiation of cattle skeletal muscle cells. Mengke Ma,Mengjie Chen,Xiaoyun Wu,Suren R. Sooranna,Qingyou Liu,Deshun Shi,Jian Wang,Hui Li. 2023

[15]Coordinated transcriptional and post-transcriptional epigenetic regulation during skeletal muscle development and growth in pigs. Du Zhang,Shumei Wu,Xinxin Zhang,Shuqiang Ren,Zhonglin Tang,Fei Gao. 2022

[16]CRISPR Screen Identifies the RNA-Binding Protein Eef1a1 as a Key Regulator of Myogenesis. Weiwei Liu,Wei Wang,Zishuai Wang,Xinhao Fan,Wangchang Li,Yuxin Huang,Xiaogan Yang,Zhonglin Tang. 2024

[17]Biology of Hippo signaling pathway: Skeletal muscle development and beyond. Shuqi Qin,Chaocheng Li,Haiyan Lu,Yulong Feng,Tao Guo,Yusong Han,Yongsheng Zhang,Zhonglin Tang. 2024

[18]A possibility of uncoupling protein 1 induction with the enhancement of myogenesis related to ruminal fermentation. Zhicheng Diao,Shunhua Jia,Erina Itoyama,Hidetugu Yoshioka,Masaru Murakami,Masayuki Funaba. 2024

[19]The miR-6240 target gene Igf2bp3 promotes myoblast fusion by enhancing myomaker mRNA stability. Yuxin Huang,Wei Wang,Xinhao Fan,Xiaoqin Liu,Weiwei Liu,Zishuai Wang,Yixing Li,Yalan Yang,Zhonglin Tang. 2025

[20]The Spatial-Temporal Alternative Splicing Profile Reveals the Functional Diversity of FXR1 Isoforms in Myogenesis. Wang, Wei,Fan, Xinhao,Liu, Weiwei,Huang, Yuxin,Zhao, Shuhong,Yang, Yalan,Tang, Zhonglin. 2025

作者其他论文 更多>>