title: Ccndbp1 is a new positive regulator of skeletal myogenesis.
abstract: Skeletal myogenesis is a multistep process in which basic helix-loop-helix (bHLH) transcription factors, such as MyoD (also known as MyoD1), bind to E-boxes and activate downstream genes. Ccndbp1 is a HLH protein that lacks a DNA-binding region, and its function in skeletal myogenesis is currently unknown. We generated Ccndbp1-null mice by using CRISPR-Cas9. Notably, in Ccndbp1-null mice, the cross sectional area of the skeletal tibialis anterior muscle was smaller, and muscle regeneration ability and grip strength were impaired, compared with those of wild type. This phenotype resembled that of myofiber hypotrophy in some human myopathies or amyoplasia. Ccndbp1 expression was upregulated during C2C12 myogenesis. Ccndbp1 overexpression promoted myogenesis, whereas knockdown of Ccndbp1 inhibited myogenic differentiation. Co-transfection of Ccndbp1 with MyoD and/or E47 (encoded by TCF3) significantly enhanced E-box-dependent transcription. Furthermore, Ccndbp1 physically associated with MyoD but not E47. These data suggest that Ccndbp1 regulates muscle differentiation by interacting with MyoD and enhancing its binding to target genes. Our study newly identifies Ccndbp1 as a positive modulator of skeletal myogenic differentiation in vivo and in vitro, providing new insights in order to decipher the complex network involved in skeletal myogenic development and related diseases.
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 51006, China Collaborative Innovation Center for Cancer Medicine, Guangzhou Key Laboratory of Healthy Aging Research, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 51006, China.
authors.forename: Bohong
authors.initials: B
authors.lastname: Chen
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 51006, China.
authors.forename: Miaoman
authors.initials: M
authors.lastname: Ye
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 51006, China.
authors.forename: Puping
authors.initials: P
authors.lastname: Liang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 51006, China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Zhangfang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 51006, China.
authors.forename: Junjiu
authors.initials: J
authors.lastname: Huang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 51006, China Collaborative Innovation Center for Cancer Medicine, Guangzhou Key Laboratory of Healthy Aging Research, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Songyang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 51006, China Collaborative Innovation Center for Cancer Medicine, Guangzhou Key Laboratory of Healthy Aging Research, Sun Yat-sen University, Guangzhou 510006, China mawenbin@mail.sysu.edu.cn.
authors.forename: Wenbin
authors.identifier: 0000-0001-8774-7593
authors.initials: W
authors.lastname: Ma
mesh_terms: D000818:Animals; D054715:Cardiotoxins / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D024721:E-Box Elements / Q000235:genetics; D055785:Gene Knockdown Techniques; D006984:Hypertrophy; D018345:Mice, Knockout; D024510:Muscle Development / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D054715:Cardiotoxins; C107359:Ccndbp1 protein, mouse; D017570:MyoD Protein; D014157:Transcription Factors
keywords: Ccndbp1; MyoD; Myogenesis; Skeletal muscle regeneration