The histone code reader Spin1 controls skeletal muscle development.

Area of Science:

• Molecular Biology
• Developmental Biology
• Genetics

Background:

• The histone code reader Spin1 has been linked to tumor formation, but its physiological roles remain largely unknown.
• Understanding Spin1's function is crucial for elucidating its involvement in both normal development and disease.

Purpose of the Study:

• To investigate the physiological functions of Spin1 in skeletal muscle development.
• To determine the impact of Spin1 ablation on myogenesis and skeletal muscle structure and function.

Main Methods:

• Generation of Spin1-deficient mice (Spin1M5) using Myf5-Cre system.
• Histological analysis of muscle tissue.
• Transcriptome analysis of limb muscle at various developmental stages.
• Genome-wide chromatin occupancy determination in primary myoblasts.

Main Results:

• Spin1 ablation in myoblast precursors leads to early postnatal lethality with severe sarcomere disorganization and necrosis.
• Surviving Spin1-deficient mice exhibit growth retardation and significant defects in major skeletal muscles.
• Transcriptome analyses reveal aberrant fetal myogenesis, deregulated skeletal muscle functional networks, and aberrant expression of titin-associated proteins.
• Identification of direct Spin1 target genes and evidence for deregulated basic helix-loop-helix transcription factor networks.

Conclusions:

• Spin1 is the first identified histone code reader critically controlling skeletal muscle development in mice.
• Defects in Spin1-deficient mice involve aberrant protein expression, glycogen metabolism, and neuromuscular junctions.
• Spin1 represents a potential therapeutic target for human skeletal muscle diseases.