Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Dec 15;88(24):11300–11304. doi: 10.1073/pnas.88.24.11300

Methylation changes in the apolipoprotein AI gene during embryonic development of the mouse.

R Shemer 1, T Kafri 1, A O'Connell 1, S Eisenberg 1, J L Breslow 1, A Razin 1
PMCID: PMC53122  PMID: 1763043

Abstract

We report here a detailed study of developmental changes in the methylation status of specific sites in a single-copy tissue-specific gene, from the germ cell through the early embryo to adult tissues. Two sites at the 5' end of the mouse apolipoprotein AI gene were unmethylated in the ovulated unfertilized oocytes and methylated in the sperm. In contrast, a third site, located upstream of the gene, was methylated and a CpG island within the gene was unmethylated in both oocyte and sperm. The methylated sites, regardless of maternal or paternal origin, underwent demethylation in the early embryo (8-16 cells) and stayed unmethylated through the late blastocyst stage. During gastrulation, non-CpG island sites underwent methylation, followed by gradual demethylation at specific sites in tissues parallel to expression of the gene (liver and intestine). The formation of the mature tissue-specific methylation pattern of the apolipoprotein AI gene, therefore, involves the following three major events: (i) erasure of the germ-cell methylation pattern (at the 8- to 16-cell stage), (ii) formation of a new methylation pattern by de novo methylation of non-CpG island sites (during gastrulation), and (iii) tissue-specific demethylation associated with the onset of expression of the gene.

Full text

PDF
11302

Images in this article

11301Image
on p.11301
11301Image
on p.11301
11302Image
on p.11302
11303Image
on p.11303

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benvenisty N., Mencher D., Meyuhas O., Razin A., Reshef L. Sequential changes in DNA methylation patterns of the rat phosphoenolpyruvate carboxykinase gene during development. Proc Natl Acad Sci U S A. 1985 Jan;82(2):267–271. doi: 10.1073/pnas.82.2.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chaillet J. R., Vogt T. F., Beier D. R., Leder P. Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis. Cell. 1991 Jul 12;66(1):77–83. doi: 10.1016/0092-8674(91)90140-t. [DOI] [PubMed] [Google Scholar]
  3. Frank D., Keshet I., Shani M., Levine A., Razin A., Cedar H. Demethylation of CpG islands in embryonic cells. Nature. 1991 May 16;351(6323):239–241. doi: 10.1038/351239a0. [DOI] [PubMed] [Google Scholar]
  4. Meehan R. R., Barlow D. P., Hill R. E., Hogan B. L., Hastie N. D. Pattern of serum protein gene expression in mouse visceral yolk sac and foetal liver. EMBO J. 1984 Aug;3(8):1881–1885. doi: 10.1002/j.1460-2075.1984.tb02062.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Monk M., Boubelik M., Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development. 1987 Mar;99(3):371–382. doi: 10.1242/dev.99.3.371. [DOI] [PubMed] [Google Scholar]
  6. Monk M. Changes in DNA methylation during mouse embryonic development in relation to X-chromosome activity and imprinting. Philos Trans R Soc Lond B Biol Sci. 1990 Jan 30;326(1235):299–312. doi: 10.1098/rstb.1990.0013. [DOI] [PubMed] [Google Scholar]
  7. Monk M. Genomic imprinting. Memories of mother and father. Nature. 1987 Jul 16;328(6127):203–204. doi: 10.1038/328203a0. [DOI] [PubMed] [Google Scholar]
  8. Razin A., Cedar H. DNA methylation and gene expression. Microbiol Rev. 1991 Sep;55(3):451–458. doi: 10.1128/mr.55.3.451-458.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Sanford J. P., Clark H. J., Chapman V. M., Rossant J. Differences in DNA methylation during oogenesis and spermatogenesis and their persistence during early embryogenesis in the mouse. Genes Dev. 1987 Dec;1(10):1039–1046. doi: 10.1101/gad.1.10.1039. [DOI] [PubMed] [Google Scholar]
  10. Shemer R., Walsh A., Eisenberg S., Breslow J. L., Razin A. Tissue-specific methylation patterns and expression of the human apolipoprotein AI gene. J Biol Chem. 1990 Jan 15;265(2):1010–1015. [PubMed] [Google Scholar]
  11. Singer-Sam J., Grant M., LeBon J. M., Okuyama K., Chapman V., Monk M., Riggs A. D. Use of a HpaII-polymerase chain reaction assay to study DNA methylation in the Pgk-1 CpG island of mouse embryos at the time of X-chromosome inactivation. Mol Cell Biol. 1990 Sep;10(9):4987–4989. doi: 10.1128/mcb.10.9.4987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Singer-Sam J., LeBon J. M., Tanguay R. L., Riggs A. D. A quantitative HpaII-PCR assay to measure methylation of DNA from a small number of cells. Nucleic Acids Res. 1990 Feb 11;18(3):687–687. doi: 10.1093/nar/18.3.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Szyf M., Tanigawa G., McCarthy P. L., Jr A DNA signal from the Thy-1 gene defines de novo methylation patterns in embryonic stem cells. Mol Cell Biol. 1990 Aug;10(8):4396–4400. doi: 10.1128/mcb.10.8.4396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wilks A., Seldran M., Jost J. P. An estrogen-dependent demethylation at the 5' end of the chicken vitellogenin gene is independent of DNA synthesis. Nucleic Acids Res. 1984 Jan 25;12(2):1163–1177. doi: 10.1093/nar/12.2.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Williams S. C., Grant S. G., Reue K., Carrasquillo B., Lusis A. J., Kinniburgh A. J. cis-acting determinants of basal and lipid-regulated apolipoprotein A-IV expression in mice. J Biol Chem. 1989 Nov 15;264(32):19009–19016. [PubMed] [Google Scholar]
  16. Yisraeli J., Adelstein R. S., Melloul D., Nudel U., Yaffe D., Cedar H. Muscle-specific activation of a methylated chimeric actin gene. Cell. 1986 Aug 1;46(3):409–416. doi: 10.1016/0092-8674(86)90661-6. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES