Poster Presentation 16th Asian Conference on Transcription 2019

Pericentromeric heterochromatin clustering is impaired in muscle atrophy (1180)

HongMin Lee 1 , Jinyoung Park 1 , Eun-Jung Cho 1
  1. Sungkyunkwan University School of Pharmacy, South Korea

During skeletal muscle development and regeneration, myogenic precursors termed satellite cells undergo several cellular and molecular changes while they differentiate to multinucleated myotubes that express a large amount of contractile muscle proteins. Such myogenic differentiation is particularly highlighted by a progressive clustering of heterochromatin that form a large repressive compartment within nucleus, called chromocenters. Meanwhile, muscle atrophy, initiated by various conditions such as aging or cancer, is characterized by a large decrease in muscle proteins and reduction of fiber diameter. When muscle atrophy undergoes, it is well described that proteolytic systems such as the ubiquitination-proteasome system (UPS) pathway or the autophagy-lysosomal system (ALS) pathway are activated, leading to decrease of contractile muscle proteins. However, it's not known whether the expression of muscle genes or the chromatin condition were altered. Therefore, we have investigated any changes in chromatin signatures in atrophy-induced muscle cells. We found that heterochromatin integrity of myotube nuclei was primarily affected during muscle atrophy. Here we show that the number of chromocenters of atrophy muscle cells were increased with heterochromatin foci being scattered. Also, H4K20me3, a heterochromatin-enriched histone mark and the histone chaperone DAXX tended to be delocalized from the chromocenter foci throughout the nucleus, suggesting that focal localization of chromatin factors and heterochromatin clustering might be affected during muscle atrophy. We further discuss the underlying mechanisms that are required for the maintenance of muscle integrity.