Distinct dynamics of parental 5-hydroxymethylcytosine during human preimplantation development regulate early lineage gene expression.
Nat Cell Biol
; 26(9): 1458-1469, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39080410
ABSTRACT
The conversion of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes represents a significant epigenetic modification, yet its role in early human embryos remains largely unknown. Here we showed that the early human embryo inherited a significant amount of 5hmCs from an oocyte, which unexpectedly underwent de novo hydroxymethylation during its growth. Furthermore, the generation of 5hmC in the paternal genome after fertilization roughly followed the maternal pattern, which was linked to DNA methylation dynamics and regions of sustained methylation. The 5hmCs persisted until the eight-cell stage and exhibited high enrichment at OTX2 binding sites, whereas knockdown of OTX2 in human embryos compromised the expression of early lineage genes. Specifically, the depletion of 5hmC affected the activation of embryonic genes, which was further evaluated by ectopically expressing mouse Tet3 in human early embryos. These findings revealed distinct dynamics of 5hmC and unravelled its multifaceted functions in early human embryonic development.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
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Regulação da Expressão Gênica no Desenvolvimento
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Metilação de DNA
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Citosina
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5-Metilcitosina
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Dioxigenases
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Desenvolvimento Embrionário
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Proteínas de Ligação a DNA
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Fatores de Transcrição Otx
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article