Letters to Nature

Nature 431, 96-99 (2 September 2004) | doi:10.1038/nature02886; Received 22 May 2004; Accepted 26 July 2004; Published online 18 August 2004

Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L

Déborah Bourc'his & Timothy H. Bestor

  1. Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, 701 West 168th Street, New York, New York 10032, USA

Correspondence to: Timothy H. Bestor Email: thb12@columbia.edu
Dnmt3L tm1Bes mutant mice are available from the Jackson Labs (http://jaxmice.jax.org/).

Mammalian genomes employ heritable cytosine methylation in the long-term silencing of retrotransposons and genes subject to genomic imprinting and X chromosome inactivation. Little is known of the mechanisms that direct cytosine methylation to specific sequences. Here we show that DNA methyltransferase 3-like (Dnmt3L (ref. 1)) is expressed in testes during a brief perinatal period in the non-dividing precursors of spermatogonial stem cells at a stage where retrotransposons undergo de novo methylation. Deletion of the Dnmt3L gene prevented the de novo methylation of both long-terminal-repeat (LTR) and non-LTR retrotransposons, which were transcribed at high levels in spermatogonia and spermatocytes. Loss of Dnmt3L from early germ cells also caused meiotic failure in spermatocytes, which do not express Dnmt3L. Whereas dispersed repeated sequences were demethylated in mutant germ cells, tandem repeats in pericentric regions were methylated normally. This result indicates that the Dnmt3L protein might have a function in the de novo methylation of dispersed repeated sequences in a premeiotic genome scanning process that occurs in male germ cells at about the time of birth.

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