Article abstract
Nature Genetics 40, 411 - 420 (2008)
Published online: 2 March 2008 | Corrected online: 16 March 2008 | doi:10.1038/ng.99
PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos
Mareike Puschendorf1, Rémi Terranova1, Erwin Boutsma2, Xiaohong Mao3,6, Kyo-ichi Isono4, Urszula Brykczynska1, Carolin Kolb1, Arie P Otte5, Haruhiko Koseki4, Stuart H Orkin3, Maarten van Lohuizen2 & Antoine H F M Peters1
Abstract
In eukaryotes, Suv39h H3K9 trimethyltransferases are required for pericentric heterochromatin formation and function. In early mouse preimplantation embryos, however, paternal pericentric heterochromatin lacks Suv39h-mediated H3K9me3 and downstream marks. Here we demonstrate Ezh2-independent targeting of maternally provided polycomb repressive complex 1 (PRC1) components to paternal heterochromatin. In Suv39h2 maternally deficient zygotes, PRC1 also associates with maternal heterochromatin lacking H3K9me3, thereby revealing hierarchy between repressive pathways. In Rnf2 maternally deficient zygotes, the PRC1 complex is disrupted, and levels of pericentric major satellite transcripts are increased at the paternal but not the maternal genome. We conclude that in early embryos, Suv39h-mediated H3K9me3 constitutes the dominant maternal transgenerational signal for pericentric heterochromatin formation. In absence of this signal, PRC1 functions as the default repressive back-up mechanism. Parental epigenetic asymmetry, also observed along cleavage chromosomes, is resolved by the end of the 8-cell stage—concurrent with blastomere polarization—marking the end of the maternal-to-embryonic transition.
- Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
- Division of Molecular Genetics and Centre for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
- Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Stem Cell Institute and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
- RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku Yokohama City, Kanagawa 230-0045, Japan.
- Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 406, 1098 SM Amsterdam, The Netherlands.
- Present address: Novartis Institutes for BioMedical Research, Inc., 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Correspondence to: Antoine H F M Peters1 e-mail: antoine.peters@fmi.ch