Imprinting mechanisms

Miguel Constância, Benjamin Pickard, Gavin Kelsey, Wolf Reik

Research output: Contribution to journalArticle

239 Citations (Scopus)
120 Downloads (Pure)

Abstract

A number of recent studies have provided new insights into mechanisms that regulate genomic imprinting in the mammalian genome. Regions of allele-specific differential methylation (DMRs) are present in all imprinted genes examined. Differential methylation is erased in germ cells at an early stage of their development, and germ-line-specific methylation imprints in DMRs are reestablished around the time of birth. After fertilization, differential methylation is retained in core DMRs despite genome-wide demethylation and de novo methylation during preimplantation and early postimplantation stages. Direct repeats near CG-rich DMRs may be involved in the establishment and maintenance of allele-specific methylation patterns. Imprinted genes tend to be clustered; one important component of clustering is enhancer competition, whereby promoters of linked imprinted genes compete for access to enhancers. Regional organization and spreading of the epigenotype during development is also important and depends on DMRs and imprinting centers. The mechanism of cis spreading of DNA methylation is not known, but precedent is provided by the Xist RNA, which results in X chromosome inactivation in cis. Reading of the somatic imprints could be carried out by transcription factors that are sensitive to methylation, or by methyl-cytosine-binding proteins that are involved in transcriptional repression through chromatin remodeling.
Original languageEnglish
Pages (from-to)881-900
Number of pages20
JournalGenome Research
Volume8
Issue number9
Publication statusPublished - Sep 1998

Keywords

  • animals
  • DNA methylation
  • gene expression regulation
  • genomic imprinting
  • germ cells
  • humans
  • RNA
  • tandem repeat sequences

Cite this

Constância, M., Pickard, B., Kelsey, G., & Reik, W. (1998). Imprinting mechanisms. Genome Research, 8(9), 881-900.