Author: Yuqing YangPublisher:
ISBN:
Category :
Languages : en
Pages : 0
Book Description
"Skeletal muscle is one of the most dynamic human tissues and it is critical for the voluntary movement of the body. Muscle function is tightly linked to its delicate structure, which is mainly composed of myofibers and connective tissues. Muscle contraction is achieved by the cooperation of diverse types of myofibers, and supported by muscle metabolism that is dependent on robust mitochondria activity. When homeostasis is disrupted, skeletal muscle exhibits various strategies to deal with the injury, depending on the severity of the injury. Muscle regeneration has strong links with the activation of a muscle stem cell transcriptional program. CCCTC-binding factor (CTCF) is an indispensable protein in vertebrates and promotes a myogenic differentiation program in muscle cell line. It is regarded as a multifunctional epigenetic regulatory protein. CTCF was first identified as a transcriptional repressor. In addition to the regulation of transcription, it also plays a critical role as a genomic architectural protein. Recent studies indicate that CTCF is involved in muscle-related diseases. However, the role of CTCF in skeletal muscle in vivo homeostasis has not been explored. Our novel study investigated whether CTCF plays a role in skeletal muscle formation and function through employing a Ctcf knockout mouse, HSACre/+; Ctcffl/fl mice. In this model, Ctcf expression is specifically reduced in skeletal muscle myonuclei, starting at 9.5 days post coitum. We found that these mice started to progressively lose weight and muscle mass at 8 weeks after birth, and demonstrated dramatic muscle wasting by 13 weeks. Meanwhile, CTCF-deficient mice also exhibit serious defects in muscle function and contraction. Furthermore, the loss of CTCF in skeletal muscles lead to signs of regeneration at 13 weeks, while these muscles only had a few degenerating myofibers. It suggests that CTCF-deficient muscle may suffer from continuous muscle injuries which trigger strong muscle regeneration. Transcriptome analysis provides insight that repression of genes involved in muscle contraction and homeostasis may underlie the muscle wasting observed in Ctcf knockout mice"--