Cell Stem Cell
Volume 11, Issue 3, 7 September 2012, Pages 333-345
Journal home page for Cell Stem Cell

Article
Carm1 Regulates Pax7 Transcriptional Activity through MLL1/2 Recruitment during Asymmetric Satellite Stem Cell Divisions

https://doi.org/10.1016/j.stem.2012.07.001Get rights and content
Under an Elsevier user license
open archive

Summary

In skeletal muscle, asymmetrically dividing satellite stem cells give rise to committed satellite cells that transcribe the myogenic determination factor Myf5, a Pax7-target gene. We identified the arginine methyltransferase Carm1 as a Pax7 interacting protein and found that Carm1 specifically methylates multiple arginines in the N terminus of Pax7. Methylated Pax7 directly binds the C-terminal cleavage forms of the trithorax proteins MLL1/2 resulting in the recruitment of the ASH2L:MLL1/2:WDR5:RBBP5 histone H3K4 methyltransferase complex to regulatory enhancers and the proximal promoter of Myf5. Finally, Carm1 is required for the induction of de novo Myf5 transcription following asymmetric satellite stem cell divisions. We defined the C-terminal MLL region as a reader domain for the recognition of arginine methylated proteins such as Pax7. Thus, arginine methylation of Pax7 by Carm1 functions as a molecular switch controlling the epigenetic induction of Myf5 during satellite stem cell asymmetric division and entry into the myogenic program.

Highlights

► Carm1 methylates Pax7 at specific arginines within the N-terminus ► Methylated Pax7 directly binds to C-terminal cleavage forms of MLL1/2 ► Methylated Pax7 recruits ASH2L:MLL1/2:WDR5:RBBP5 H3K4 methyltransferase complex ► Pax7-Carm1 is required for Myf5 expression following asymmetric stem cell division

Cited by (0)