von Walden Ferdinand, Fernandez-Gonzalo Rodrigo, Pingel Jessica, McCarthy John, Stål Per, Pontén Eva
Division of Pediatric Neurology/Orthopedics/Rheumatology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology, University of Kentucky, Lexington, KY, United States.
Front Pediatr. 2020 Jun 3;8:236. doi: 10.3389/fped.2020.00236. eCollection 2020.
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. 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. 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. 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.
脑瘫（CP）是儿童中最常见的运动障碍。脑瘫患者的骨骼肌通常虚弱、纤细且僵硬。核糖体DNA（rDNA）启动子处的表观遗传变化是否参与这种失调尚不清楚。从19名脑瘫儿童和10名发育正常（TD）的对照儿童中采集骨骼肌样本。使用Agena Epityper Mass阵列分析rDNA启动子的甲基化，并通过qRT-PCR分析基因表达。与TD相比，CP患者肱二头肌的核糖体生物合成受到抑制。CP组和TD组rDNA启动子的平均甲基化没有差异，但在CP组中与肘屈肌挛缩呈负相关。我们观察到CP组中rDNA启动子甲基化与肌肉挛缩程度之间存在负相关。与受影响较小的儿童相比，运动障碍更严重的脑瘫儿童rDNA启动子的甲基化较少。这一发现表明神经输入和自主肌肉运动对于肱二头肌启动子甲基化的发生很重要。
