Tet1 controls meiosis by regulating meiotic gene expression

Abstract

Meiosis is a germ cell-specific cell division process through which haploid gametes are produced for sexual reproduction1. Prior to initiation of meiosis, mouse primordial germ cells (PGCs) undergo a series of epigenetic reprogramming steps2,3, including global erasure of DNA methylation on the 5-position of cytosine (5mC) at CpG4,5. Although several epigenetic regulators, such as Dnmt3l, histone methyltransferases G9a and Prdm9, have been reported to be critical for meiosis6, little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. Using a loss of function approach, here we demonstrate that the 5mC-specific dioxygenase Tet1 plays an important role in regulating meiosis in mouse oocytes. Tet1 deficiency significantly reduces female germ cell numbers and fertility. Univalent chromosomes and unresolved DNA double strand breaks are also observed in Tet1-deficient oocytes. Tet1 deficiency does not greatly affect the genome-wide demethylation that takes place in PGCs but leads to defective DNA demethylation and decreased expression of a subset of meiotic genes. Our study thus establishes a function for Tet1 in meiosis and meiotic gene activation in female germ cells.