Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader.
Nucleic Acids Res
; 52(10): 5529-5548, 2024 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-38512058
ABSTRACT
The process of induced pluripotent stem cells (iPSCs) reprogramming involves several crucial events, including the mesenchymal-epithelial transition (MET), activation of pluripotent genes, metabolic reprogramming, and epigenetic rewiring. Although these events intricately interact and influence each other, the specific element that regulates the reprogramming network remains unclear. Dux, a factor known to promote totipotency during the transition from embryonic stem cells (ESC) to 2C-like ESC (2CLC), has not been extensively studied in the context of iPSC reprogramming. In this study, we demonstrate that the modification of H3K18la induced by Dux overexpression controls the metabolism-H3K18la-MET network, enhancing the efficiency of iPSC reprogramming through a metabolic switch and the recruitment of p300 via its C-terminal domain. Furthermore, our proteomic analysis of H3K18la immunoprecipitation experiment uncovers the specific recruitment of Brg1 during reprogramming, with both H3K18la and Brg1 being enriched on the promoters of genes associated with pluripotency and epithelial junction. In summary, our study has demonstrated the significant role of Dux-induced H3K18la in the early reprogramming process, highlighting its function as a potent trigger. Additionally, our research has revealed, for the first time, the binding of Brg1 to H3K18la, indicating its role as a reader of histone lactylation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Histonas
/
Proteínas de Homeodomínio
/
Reprogramação Celular
/
Células-Tronco Pluripotentes Induzidas
/
Transição Epitelial-Mesenquimal
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China