Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat.
Nat Commun
; 12(1): 6838, 2021 11 25.
Article
in En
| MEDLINE
| ID: mdl-34824202
Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adipose Tissue, Brown
/
Muscle Development
/
Epigenesis, Genetic
/
Histone Demethylases
/
Diet, High-Fat
/
DNA (Cytosine-5-)-Methyltransferase 1
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2021
Document type:
Article
Affiliation country:
United States
Country of publication:
United kingdom