https://mcb.berkeley.edu/courses/mcb230/WEB/PAPERS/jenuwein%20cell%20suv39%20genome%20stability%20copy.pdf

Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability.

Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.

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.

Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L.

Oct4-induced pluripotency in adult neural stem cells

In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11-dependent double-strand breaks (DSBs), a process that precedes homologous synapsis. Here we use an antibody specific for a phosphorylated histone (gamma-H2AX, which marks the sites of DSBs) to investigate the timing, distribution and Spo11-dependence of meiotic DSBs in the mouse. We show that, as in yeast, recombination in the mouse is initiated by Spo11-dependent DSBs that form during leptotene. Loss of gamma-H2AX staining (which in irradiated somatic cells is temporally linked with DSB repair) is temporally and spatially correlated with synapsis, even when this synapsis is 'non-homologous'.

Recombinational DNA double-strand breaks in mice precede synapsis

A.H.F.M. Peters (corresponding author), A.W. Plug, M.J. van Vugt and P. de Boer are at the Department of Genetics, Wageningen Institute of Animal Sciences, Wageningen Agricultural University, Dreijenlaan 2, NL-6703 HA Wageningen, The Netherlands. Tel: ( 31) 317 483147; Fax: ( 31) 317 483929; Email: Antoine.Peters@alg.vf.wau.nl. A.W. Plug is now at the Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.

M.J. van Vugt

Papers

A drying-down technique for the spreading of mammalian meiocytes from the male and female germline.