Histone methylation defines epigenetic asymmetry in the mouse zygote.

The oocyte cytoplasm regulates and enhances the epigenetic asymmetry between parental genomes and, consequently, functional differences observed between them during development in mammals. Here we demonstrate a preferential interaction of HP1beta with the maternal genome immediately after fertilisation in the mouse zygote, which also shows a high level of lysine 9-methylated histone H3. In contrast, the paternal genome has neither HP1beta binding nor methylated histone H3 at these early stages. Paternal binding of HP1beta is only detected at the pronuclear stage, prior to the appearance of lysine 9-methylated histone H3. The early recruitment of heterochromatic factors specifically to the maternal genome could explain the preferential DNA demethylation of the paternal genome in the zygote.

[1]  E. Selker,et al.  A histone H3 methyltransferase controls DNA methylation in Neurospora crassa , 2001, Nature.

[2]  S. Baylin,et al.  Dnmt3a and Dnmt3b Are Transcriptional Repressors That Exhibit Unique Localization Properties to Heterochromatin* , 2001, The Journal of Biological Chemistry.

[3]  Wendy Dean,et al.  Dynamic reprogramming of DNA methylation in the early mouse embryo. , 2002, Developmental biology.

[4]  Andrew J. Bannister,et al.  Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain , 2001, Nature.

[5]  Matthias Merkenschlager,et al.  Association of Transcriptionally Silent Genes with Ikaros Complexes at Centromeric Heterochromatin , 1997, Cell.

[6]  W. Reik,et al.  Evolution of imprinting mechanisms: the battle of the sexes begins in the zygote , 2001, Nature Genetics.

[7]  J. Renard,et al.  Differential H4 acetylation of paternal and maternal chromatin precedes DNA replication and differential transcriptional activity in pronuclei of 1-cell mouse embryos. , 1997, Development.

[8]  Yanbo Xu,et al.  Reconstitution of Enhancer Function in Paternal Pronuclei of One-Cell Mouse Embryos , 2001, Molecular and Cellular Biology.

[9]  B. Pickard,et al.  Epigenetic targeting in the mouse zygote marks DNA for later methylation: a mechanism for maternal effects in development , 2001, Mechanisms of Development.

[10]  F. Aoki,et al.  Regulation of transcriptional activity during the first and second cell cycles in the preimplantation mouse embryo. , 1997, Developmental biology.

[11]  A. Bird,et al.  Absence of genome-wide changes in DNA methylation during development of the zebrafish , 1999, Nature Genetics.

[12]  T. Bestor,et al.  Properties and localization of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting. , 1992, Genes & development.

[13]  W. Reik,et al.  Active demethylation of the paternal genome in the mouse zygote , 2000, Current Biology.

[14]  W Dean,et al.  Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Surani,et al.  Imprinting and the Epigenetic Asymmetry Between Parental Genomes , 2001, Science.

[16]  Andrew J. Bannister,et al.  Rb targets histone H3 methylation and HP1 to promoters , 2001, Nature.

[17]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[18]  F. Ding,et al.  Genomic Imprinting Disrupted by a Maternal Effect Mutation in the Dnmt1 Gene , 2001, Cell.

[19]  J. Walter,et al.  Maternal methylation imprints on human chromosome 15 are established during or after fertilization , 2001, Nature Genetics.

[20]  J. Vonesch,et al.  The putative nuclear receptor mediator TIF1alpha is tightly associated with euchromatin. , 1999, Journal of cell science.

[21]  J. Walter,et al.  Embryogenesis: Demethylation of the zygotic paternal genome , 2000, Nature.