Temporal and spatial regulation of H19 imprinting in normal and uniparental mouse embryos

Hiroyuki Sasaki, Anne C. Ferguson-Smith, Alisa S.W. Shum, Sheila C. Barton, M. Azim Surani

研究成果: Contribution to journalArticle査読

134 被引用数 (Scopus)

抄録

The mouse H19 gene is imprinted so that the paternal copy is both methylated and repressed during fetal development. However, the CpG-rich promoter region encompassing the transcription start is not methylated in sperm; this region must therefore become methylated postzygotically. We first examined the timing of DNA methylation of this region and the corresponding expression of H19. Both parental copies are initially undermethylated in blastocysts and the paternal copy then becomes fully methylated in the embryo around implantation; this methylation is more protracted in the extraembryonic lineages, especially in the trophoblast. By contrast to the lineage-dependent methylation, we observed exclusive expression of the maternal copy in preimplantation embryos and in all the lineages of early postimplantation embryos although variability may exist in cultured embryos. This indicates that methylation of the CpG-rich promoter is not a prerequisite for the paternal repression. We then examined whether methylation and expression occurs appropriately in the absence of a maternal or a paternal genome. Both H19 copies in androgenetic embryos are fully methylated while they are unmethylated in parthenogenetic embryos. This correlates with the lack of expression in androgenetic embryos but expression in parthenogenetic embryos. However, the androgenetic trophoblast was exceptional as it shows reduced methylation and expresses H19. These results suggest that promoter methylation is not the primary inactivation mechanism but is a stabilizing factor. Differential methylation in the more upstream region, which is established in the gametes, is a likely candidate for the gametic signal and may directly control H19 activity.

本文言語英語
ページ(範囲)4195-4202
ページ数8
ジャーナルDevelopment
121
12
出版ステータス出版済み - 12 1 1995

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 発生生物学

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