FoxA-dependent demethylation of DNA initiates epigenetic memory of cellular identity.
Dev Cell
; 56(5): 602-612.e4, 2021 03 08.
Article
em En
| MEDLINE
| ID: mdl-33636105
ABSTRACT
Tissue-specific DNA methylation patterns are created by transcription factors that recruit methylation and demethylation enzymes to cis-regulatory elements. To date, it is not known whether transcription factors are needed to continuously maintain methylation profiles in development and mature tissues or whether they only establish these marks during organ development. We queried the role of the pioneer factor FoxA in generating hypomethylated DNA at liver enhancers. We discovered a set of FoxA-binding sites that undergo regional, FoxA-dependent demethylation during organ development. Conditional ablation of FoxA genes in the adult liver demonstrated that continued FoxA presence was not required to maintain the hypomethylated state, even when massive cell proliferation was induced. This study provides strong evidence for the stable, epigenetic nature of tissue-specific DNA methylation patterns directed by lineage-determining transcription factors during organ development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Elementos Facilitadores Genéticos
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Metilação de DNA
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Epigênese Genética
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Fator 3-alfa Nuclear de Hepatócito
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Fator 3-beta Nuclear de Hepatócito
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Fígado
Limite:
Animals
Idioma:
En
Revista:
Dev Cell
Assunto da revista:
EMBRIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos