5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming

• Tipo: Artigo em Revista Científica Internacional
• Data: 2011

Autores

Wossidlo, M (Autor) Outra; Nakamura, T (Autor) Outra; Lepikhov, K (Autor) Outra; Marques, CJ (Autor) FMUP; Zakhartchenko, V (Autor) Outra; Boiani, M (Autor) Outra; Arand, J (Autor) Outra; Nakano, T (Autor) Outra; Reik, W (Autor) Outra; Walter, J (Autor) Outra

Revista

Título: Nature Communications

Vol. 2

Página Final: 241

ISSN: 2041-1723

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 613 Citações

Scopus - 651 Citações

Outras Informações

ID Authenticus: P-009-FM0

DOI: 10.1038/ncomms1240

Abstract (EN): The epigenomes of early mammalian embryos are extensively reprogrammed to acquire a totipotent developmental potential. A major initial event in this reprogramming is the active loss/demethylation of 5-methylcytosine (5mC) in the zygote. Here, we report on findings that link this active demethylation to molecular mechanisms. We detect 5-hydroxymethylcytosine (5hmC) as a novel modification in mouse, bovine and rabbit zygotes. On zygotic development 5hmC accumulates in the paternal pronucleus along with a reduction of 5mC. A knockdown of the 5hmC generating dioxygenase Tet3 simultaneously affects the patterns of 5hmC and 5mC in the paternal pronucleus. This finding links the loss of 5mC to its conversion into 5hmC. The maternal pronucleus seems to be largely protected against this mechanism by PGC7/Dppa3/Stella, as in PGC7 knockout zygotes 5mC also becomes accessible to oxidation into 5hmC. In summary, our data suggest an important role of 5hmC and Tet3 for DNA methylation reprogramming processes in the mammalian zygote.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8