Abstract-Text (inkl. Referenzen)

Introduction: DNA methylation is involved in dynamic changes of muscle development. In the present study, we investigated DNA methylation alterations in muscle-related pathologies.

Methodology and Result: Using Illumina Infinium HumanMethylationEPIC BeadChip (850k) arrays, we compared the muscle methylomes of inclusion body myositis (IBM), polymyositis (PM), amyloid later sclerosis (ALS) and multi-minicore myopathy (MMC) to healthy muscles. From unsupervised t-SNE clustering, each neuromuscular entity formed cluster characterized by distinct DNA methylation patterns. Gene ontology analysis revealed that in IBM, the hypermethylation probes are enriched in biological processes such as sarcomere organization, actin filament organization and muscle contraction; hypomethylation probes are enriched in T cell receptor signaling, antigen processing and presentation, and apoptotic process factors. These patterns are in accordance with the pathological hallmarks of IBM. In ALS, the hypermethylation is enriched in branching morphogenesis of nerves, gap junction assembly, and neurotransmitter catabolic processes; the hypomethylation is enriched in muscle contraction, myofibril assembly, and sarcomere organization factors. These alterations in part reflect the compensatory efforts of muscle fibers in response to denervation in ALS.

Conclusion: In conclusion, we demonstrate that muscle methylome data is able to provide global insight into the fundamental biological changes in the muscle.