Glis1 facilitates induction of pluripotency via an epigenome-metabolome-epigenome signalling cascade.
Nat Metab
; 2(9): 882-892, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32839595
ABSTRACT
Somatic cell reprogramming provides insight into basic principles of cell fate determination, which remain poorly understood. Here we show that the transcription factor Glis1 induces multi-level epigenetic and metabolic remodelling in stem cells that facilitates the induction of pluripotency. We find that Glis1 enables reprogramming of senescent cells into pluripotent cells and improves genome stability. During early phases of reprogramming, Glis1 directly binds to and opens chromatin at glycolytic genes, whereas it closes chromatin at somatic genes to upregulate glycolysis. Subsequently, higher glycolytic flux enhances cellular acetyl-CoA and lactate levels, thereby enhancing acetylation (H3K27Ac) and lactylation (H3K18la) at so-called 'second-wave' and pluripotency gene loci, opening them up to facilitate cellular reprogramming. Our work highlights Glis1 as a powerful reprogramming factor, and reveals an epigenome-metabolome-epigenome signalling cascade that involves the glycolysis-driven coordination of histone acetylation and lactylation in the context of cell fate determination.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Transducción de Señal
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Proteínas de Unión al ADN
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Metaboloma
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Células Madre Pluripotentes Inducidas
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Epigenoma
Límite:
Animals
Idioma:
En
Revista:
Nat Metab
Año:
2020
Tipo del documento:
Article