Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/104323
Title: DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins
Authors: Sailani, M. Reza
Santoni, Federico A.
Letourneau, Audrey
Borel, Christelle
Makrythanasis, Periklis
Hibaoui, Youssef
Popadin, Konstantin
Bonilla, Ximena
Guipponi, Michel
Gehrig, Corinne
Vannier, Anne
Carre-Pigeon, Frederique
Feki, Anis
Nizetic, Dean
Antonarakis, Stylianos E.
Keywords: Homeobox
Fibroblasts
Epigenetics
Induced pluripotent stem cells
Chromosome 21
Morphogenesis
Twins
DNA methylation
Issue Date: 2015
Source: Sailani, M. R., Santoni, F. A., Letourneau, A., Borel, C., Makrythanasis, P., Hibaoui, Y., et al. (2015). DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins. PLOS ONE, 10(8), e0135555-.
Series/Report no.: PLOS ONE
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.
URI: https://hdl.handle.net/10356/104323
http://hdl.handle.net/10220/38815
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0135555
Rights: © 2015 Sailani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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