Stage-specific roles for tet1 and tet2 in DNA demethylation in primordial germ cells.
Cell Stem Cell
; 12(4): 470-8, 2013 Apr 04.
Article
em En
| MEDLINE
| ID: mdl-23415914
ABSTRACT
Primordial germ cells (PGCs) undergo dramatic rearrangements to their methylome during embryogenesis, including initial genome-wide DNA demethylation that establishes the germline epigenetic ground state. The role of the 5-methylcytosine (5mC) dioxygenases Tet1 and Tet2 in the initial genome-wide DNA demethylation process has not been examined directly. Using PGCs differentiated from either control or Tet2(-/-); Tet1 knockdown embryonic stem cells (ESCs), we show that in vitro PGC (iPGC) formation and genome-wide DNA demethylation are unaffected by the absence of Tet1 and Tet2, and thus 5-hydroxymethylcytosine (5hmC). However, numerous promoters and gene bodies were hypermethylated in mutant iPGCs, which is consistent with a role for 5hmC as an intermediate in locus-specific demethylation. Altogether, our results support a revised model of PGC DNA demethylation in which the first phase of comprehensive 5mC loss does not involve 5hmC. Instead, Tet1 and Tet2 have a locus-specific role in shaping the PGC epigenome during subsequent development.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
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Metilação de DNA
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Proteínas de Ligação a DNA
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Células Germinativas
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article