title: Analysis of DNA methylation acquisition at the imprinted Dlk1 locus reveals asymmetry at CpG dyads.
abstract: BACKGROUND
  Differential distribution of DNA methylation on the parental alleles of imprinted genes distinguishes the alleles from each other and dictates their parent of origin-specific expression patterns. While differential DNA methylation at primary imprinting control regions is inherited via the gametes, additional allele-specific DNA methylation is acquired at secondary sites during embryonic development and plays a role in the maintenance of genomic imprinting. The precise mechanisms by which this somatic DNA methylation is established at secondary sites are not well defined and may vary as methylation acquisition at these sites occurs at different times for genes in different imprinting clusters.
  
  
  RESULTS
  In this study, we show that there is also variability in the timing of somatic DNA methylation acquisition at multiple sites within a single imprinting cluster. Paternal allele-specific DNA methylation is initially acquired at similar stages of post-implantation development at the linked Dlk1 and Gtl2 differentially methylated regions (DMRs). In contrast, unlike the Gtl2-DMR, the maternal Dlk1-DMR acquires DNA methylation in adult tissues.
  
  
  CONCLUSIONS
  These data suggest that the acquisition of DNA methylation across the Dlk1/Gtl2 imprinting cluster is variable. We further found that the Dlk1 differentially methylated region displays low DNA methylation fidelity, as evidenced by the presence of hemimethylation at approximately one-third of the methylated CpG dyads. We hypothesize that the maintenance of DNA methylation may be less efficient at secondary differentially methylated sites than at primary imprinting control regions.
authors.affiliation: Department of Biology, Bryn Mawr College, 101 N. Merion Avenue, Bryn Mawr, PA 19010-2899, USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Gagne
authors.affiliation: Department of Biology, Bryn Mawr College, 101 N. Merion Avenue, Bryn Mawr, PA 19010-2899, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Hochman
authors.affiliation: Department of Biology, Bryn Mawr College, 101 N. Merion Avenue, Bryn Mawr, PA 19010-2899, USA.
authors.forename: Mahvish
authors.initials: M
authors.lastname: Qureshi
authors.affiliation: Department of Biology, Bryn Mawr College, 101 N. Merion Avenue, Bryn Mawr, PA 19010-2899, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: Tong
authors.affiliation: Department of Biology, Bryn Mawr College, 101 N. Merion Avenue, Bryn Mawr, PA 19010-2899, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Arbon
authors.affiliation: Department of Biology, Bryn Mawr College, 101 N. Merion Avenue, Bryn Mawr, PA 19010-2899, USA.
authors.forename: Kayla
authors.initials: K
authors.lastname: McDaniel
authors.affiliation: Department of Biology, Bryn Mawr College, 101 N. Merion Avenue, Bryn Mawr, PA 19010-2899, USA.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Davis
keywords: DNA methylation; Dlk1; Epigenetics; Genomic imprinting; Secondary DMR