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PMID:18311137

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Citation

Puschendorf, M, Terranova, R, Boutsma, E, Mao, X, Isono, K, Brykczynska, U, Kolb, C, Otte, AP, Koseki, H, Orkin, SH, van Lohuizen, M and Peters, AH (2008) PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. Nat. Genet. 40:411-20

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.

Links

PubMed Online version:10.1038/ng.99

Keywords

Animals; Apoptosis/physiology; Blastomeres/metabolism; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Embryo, Mammalian/metabolism; Embryo, Mammalian/ultrastructure; Embryonic Development/physiology; Female; Fluorescent Antibody Technique; Genomic Imprinting; Heterochromatin/physiology; Heterochromatin/ultrastructure; Histone-Lysine N-Methyltransferase/genetics; Histone-Lysine N-Methyltransferase/physiology; Integrases/metabolism; Male; Methyltransferases/physiology; Mice/embryology; Mice, Inbred C57BL; Mice, Knockout; Oocytes/metabolism; Polycomb Repressive Complex 1; Polycomb Repressive Complex 2; Polycomb-Group Proteins; Proteins/genetics; Proteins/physiology; Repressor Proteins/physiology; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; Transgenes/physiology; Ubiquitin-Protein Ligases

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:BMI1

located_in

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CBX2

located_in

GO:0000791: euchromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CBX2

located_in

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:EZH2

acts_upstream_of_or_within

GO:0071168: protein localization to chromatin

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3805309

P

Seeded From UniProt

complete

MOUSE:EZH2

acts_upstream_of_or_within

GO:0070734: histone H3-K27 methylation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1858961

P

Seeded From UniProt

complete

MOUSE:RING2

located_in

GO:0000791: euchromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RING2

located_in

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PHC2

located_in

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BMI1

part_of

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RING2

part_of

GO:0000791: euchromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RING2

part_of

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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