Stage-specific roles for tet1 and tet2 in DNA demethylation in primordial germ cells. uri icon

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 invitro 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.

published proceedings

  • Cell Stem Cell

altmetric score

  • 1.85

author list (cited authors)

  • Vincent, J. J., Huang, Y., Chen, P., Feng, S., Calvopia, J. H., Nee, K., ... Clark, A. T.

citation count

  • 145

complete list of authors

  • Vincent, John J||Huang, Yun||Chen, Pao-Yang||Feng, Suhua||Calvopiña, Joseph H||Nee, Kevin||Lee, Serena A||Le, Thuc||Yoon, Alexander J||Faull, Kym||Fan, Guoping||Rao, Anjana||Jacobsen, Steven E||Pellegrini, Matteo||Clark, Amander T

publication date

  • January 2013