Muscle regeneration controlled by a designated DNA dioxygenase.
Cell Death Dis
; 12(6): 535, 2021 05 25.
Article
in En
| MEDLINE
| ID: mdl-34035232
ABSTRACT
Tet dioxygenases are responsible for the active DNA demethylation. The functions of Tet proteins in muscle regeneration have not been well characterized. Here we find that Tet2, but not Tet1 and Tet3, is specifically required for muscle regeneration in vivo. Loss of Tet2 leads to severe muscle regeneration defects. Further analysis indicates that Tet2 regulates myoblast differentiation and fusion. Tet2 activates transcription of the key differentiation modulator Myogenin (MyoG) by actively demethylating its enhancer region. Re-expressing of MyoG in Tet2 KO myoblasts rescues the differentiation and fusion defects. Further mechanistic analysis reveals that Tet2 enhances MyoD binding by demethylating the flanking CpG sites of E boxes to facilitate the recruitment of active histone modifications and increase chromatin accessibility and activate its transcription. These findings shed new lights on DNA methylation and pioneer transcription factor activity regulation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Regeneration
/
Dioxygenases
/
DNA-Binding Proteins
/
Muscles
Limits:
Animals
Language:
En
Journal:
Cell Death Dis
Year:
2021
Document type:
Article
Affiliation country:
China