Epigenetic Marks at the Ribosomal DNA Promoter in Skeletal Muscle Are Negatively Associated With Degree of Impairment in Cerebral Palsy

Frontiers in Pediatrics

article

Ferdinand von Walden¹  Rodrigo Fernandez-Gonzalo⁴  Jessica Pingel⁵  John McCarthy²  Per Stål⁶  Eva Pontén¹ 

[1] Division of Pediatric Neurology/Orthopedics/Rheumatology, Department of Women's and Children's Health, Karolinska Institutet;Department of Physiology, University of Kentucky, United States;Center for Muscle Biology, University of Kentucky, United States;Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, and Unit of Clinical Physiology, Karolinska University Hospital;Department of Neuroscience, University of Copenhagen;Laboratory of Muscle Biology, Department of Integrative Medical Biology, Umeå University

关键词: cerebral palsy;    skeletal muscle;    epigenetics;    ribosome biogenesis;    DNA methylation;   

DOI  :  10.3389/fped.2020.00236

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Introduction: Cerebral palsy (CP) is the most common motor impairment in children. Skeletal muscles in individuals with CP are typically weak, thin, and stiff. Whether epigenetic changes at the ribosomal DNA (rDNA) promoter are involved in this dysregulation remains unknown. Methods: Skeletal muscle samples were collected from 19 children with CP and 10 typically developed (TD) control children. Methylation of the rDNA promoter was analyzed using the Agena Epityper Mass array and gene expression by qRT-PCR. Results: Biceps brachii muscle ribosome biogenesis was suppressed in CP as compared to TD. Average methylation of the rDNA promoter was not different between CP and TD but negatively correlated to elbow flexor contracture in the CP group. Discussions: We observed a negative correlation between rDNA promoter methylation and degree of muscle contracture in the CP group. Children with CP with more severe motor impairment had less methylation of the rDNA promoter compared to less affected children. This finding suggests the importance of neural input and voluntary muscle movements for promoter methylation to occur in the biceps muscle.

【 授权许可】

CC BY