RCOR1 promotes myoblast differentiation and muscle regeneration

Area of Science:

• Muscle stem cell biology
• Epigenetics
• Skeletal muscle regeneration

Background:

• RCOR proteins are transcription corepressors regulating histone demethylase LSD1 and HDACs.
• LSD1's role in skeletal muscle is known, but RCOR family's role in myogenesis is unclear.

Purpose of the Study:

• Investigate the role of RCOR1 in myogenesis and skeletal muscle regeneration.
• Elucidate the mechanisms underlying RCOR1's function in myoblasts.

Main Methods:

• RCOR1 expression analysis in myoblasts and during muscle regeneration.
• RCOR1 silencing using siRNA in myoblasts.
• Assessed myoblast differentiation, proliferation, and fusion markers (myogenin, MyHC, P21).
• Investigated RCOR1 interaction with LSD1 and MyoD.
• Utilized a mouse model of skeletal muscle injury.

Main Results:

• RCOR1 is highly expressed in proliferating myoblasts and activated satellite cells.
• RCOR1 depletion impairs myoblast differentiation, fusion, and proliferation via P21.
• RCOR1 interacts with LSD1, stabilizing it in myoblasts.
• LSD1 overexpression rescues RCOR1 depletion effects on differentiation.
• RCOR1 depletion in vivo impairs satellite cell activation and muscle regeneration.

Conclusions:

• RCOR1 is a novel positive regulator of myogenesis.
• RCOR1 functions in concert with LSD1 to promote skeletal muscle regeneration.
• RCOR1 regulates myoblast proliferation and differentiation through independent mechanisms.