Myocyte enhancer factor 2A promotes proliferation and its inhibition attenuates myogenic differentiation via myozenin 2 in bovine skeletal muscle myoblast

Ya-Ning Wang; Wu-Cai Yang; Pei-Wei Li; Hong-Bao Wang; Ying-Ying Zhang; Lin-Sen Zan

doi:10.1371/journal.pone.0196255

Myocyte enhancer factor 2A promotes proliferation and its inhibition attenuates myogenic differentiation via myozenin 2 in bovine skeletal muscle myoblast

PLoS One. 2018 Apr 26;13(4):e0196255. doi: 10.1371/journal.pone.0196255. eCollection 2018.

Authors

Ya-Ning Wang^{1

2}, Wu-Cai Yang^{1

2}, Pei-Wei Li^{1

2}, Hong-Bao Wang^{1

2}, Ying-Ying Zhang³, Lin-Sen Zan^{1

2

4}

Affiliations

¹ College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
² National Beef Cattle Improvement Center in China, Yangling, Shaanxi, P. R. China.
³ Animal Husbandry and Veterinary Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai, P. R. China.
⁴ National and Provincial Joint Engineering Research Center of Modern Cattle Biotechnology and Applications, Yangling, Shaanxi, P. R. China.

Abstract

Myocyte enhancer factor 2A (MEF2A) is widely distributed in various tissues or organs and plays crucial roles in multiple biological processes. To examine the potential effects of MEF2A on skeletal muscle myoblast, the functional role of MFE2A in myoblast proliferation and differentiation was investigated. In this study, we found that the mRNA expression level of Mef2a was dramatically increased during the myogenesis of bovine skeletal muscle primary myoblast. Overexpression of MEF2A significantly promoted myoblast proliferation, while knockdown of MEF2A inhibited the proliferation and differentiation of myoblast. RT-PCR and western blot analysis revealed that this positive effect of MEF2A on the proliferation of myoblast was carried out by triggering cell cycle progression by activating CDK2 protein expression. Besides, MEF2A was found to be an important transcription factor that bound to the myozenin 2 (MyoZ2) proximal promoter and performed upstream of MyoZ2 during myoblast differentiation. This study provides the first experimental evidence that MEF2A is a positive regulator in skeletal muscle myoblast proliferation and suggests that MEF2A regulates myoblast differentiation via regulating MyoZ2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae / genetics
Animals
Cattle
Cell Cycle
Cell Differentiation
Cell Proliferation
Flow Cytometry
Gene Expression Regulation
MEF2 Transcription Factors / physiology*
Muscle Development
Muscle Proteins / physiology
Muscle, Skeletal / physiology*
Myoblasts, Skeletal / physiology*
Myoblasts, Skeletal / ultrastructure*
Promoter Regions, Genetic
RNA, Small Interfering / metabolism

Substances

MEF2 Transcription Factors
Muscle Proteins
RNA, Small Interfering

Grants and funding

This work was supported by 1. National Modern Agricultural Industry Special Program (Grant No. CARS-38) is funded by Ministry of Agriculture of the People’s Republic of China (URL: http://www.moa.gov.cn/) and Ministry of Finance of the People’s Republic of China (URL: http://www.mof.gov.cn/index.htm), Lin-Sen Zan received the funding; 2. National 863 Program of China (Grant No. 2013AA102505) is funded by Ministry of Science and Technology of the People’s Republic of China (URL: http://www.most.gov.cn/), Lin-Sen Zan received the funding; 3. National Science and Technology Support Projects (Grant No. 2015BAD03B04) is funded by Ministry of Science and Technology of the People’s Republic of China (URL: http://www.most.gov.cn/), Lin-Sen Zan received the funding; 4. Shaanxi Technological Innovation Engineering Program (Grant No. 2014KTZB02-02-01) is funded by Department of Science and Technology of Shaanxi Province (URL: http://www.sninfo.gov.cn), Lin-Sen Zan received the funding; 5. the National Natural Science Foundation of China (Grant No. 31501937) is funded by National Natural Science Foundation of China (URL: http://www.nsfc.gov.cn/), Ying-Ying Zhang received the funding; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.