• Home
  1. Home
  2. DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins
Scientific article
OA Policy
English

DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins

Contributors

Sailani, Mohammad Reza; Santoni, Federico; Letourneau, Audrey; Borel, Christelle; Makrythanasis, Periklis; Hibaoui, Youssef; Popadin, Konstantin; Bonilla Bustillo, Ximena; Guipponi, Michel; Gehrig, Corinne; Vannier, Anne; Carre-Pigeon, Frederique; Feki, Anis; Nizetic, Dean; Antonarakis, Stylianos

Published in

PloS one, vol. 10, no. 8, e0135555

Publication date

2015

Abstract

DNA methylation is essential in mammalian development. We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in Down syndrome (DS). In order to determine the methylation differences in T21 without interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21. We also used skin fibroblasts from MZ twins concordant for T21, normal MZ twins without T21, and unrelated normal and T21 individuals. Reduced Representation Bisulfite Sequencing (RRBS) revealed 35 differentially methylated promoter regions (DMRs) (Absolute methylation differences = 25%, FDR < 0.001) in MZ twins discordant for T21 that have also been observed in comparison between unrelated normal and T21 individuals. The identified DMRs are enriched for genes involved in embryonic organ morphogenesis (FDR = 1.60 e -03) and include genes of the HOXB and HOXD clusters. These DMRs are maintained in iPS cells generated from this twin pair and are correlated with the gene expression changes. We have also observed an increase in DNA methylation level in the T21 methylome compared to the normal euploid methylome. This observation is concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) observed in the iPSC of the T21 versus normal twin. Altogether, the results of this study highlight the epigenetic effects of the extra chromosome 21 in T21 on loci outside of this chromosome that are relevant to DS associated phenotypes.

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

SAILANI, Mohammad Reza et al. DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins. In: PloS one, 2015, vol. 10, n° 8, p. e0135555. doi: 10.1371/journal.pone.0135555

Main files (1)

Article (Published version)
CC BY

Identifiers

Journal ISSN

1932-6203
677views
481downloads

Technical informations

Creation

13/11/2015 16:05:00

First validation

13/11/2015 16:05:00

Update

14/03/2023 23:50:44

Status update

14/03/2023 23:50:44

Last indexation

31/10/2024 01:56:44
All rights reserved by Archive ouverte UNIGE and the University of Geneva
OpenAIRE Indexed & Validated