UNIGE document Scientific Article
previous document  unige:42268  next document
add to browser collection

Domains of genome-wide gene expression dysregulation in Down's syndrome

Gonzalez, David
Kind, Jop
Thurman, Robert
show hidden authors show all authors [1 - 28]
Published in Nature. 2014, vol. 508, no. 7496, p. 345-50
Abstract Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down's syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.
Keywords AnimalsCells, CulturedChromatin/chemistry/metabolismChromosomes, Human, Pair 21/geneticsChromosomes, Mammalian/geneticsDNA Replication TimingDown Syndrome/genetics/pathologyFemaleFetus/cytologyFibroblastsGene Expression Regulation/geneticsGenome/geneticsHistones/chemistry/metabolismHumansInduced Pluripotent Stem Cells/metabolismLysine/metabolismMaleMethylationMiceTranscriptome/geneticsTwins, Monozygotic/genetics
PMID: 24740065
Full text
Article (Published version) (3.4 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research group Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
(ISO format)
LETOURNEAU, Audrey et al. Domains of genome-wide gene expression dysregulation in Down's syndrome. In: Nature, 2014, vol. 508, n° 7496, p. 345-50. doi: 10.1038/nature13200 https://archive-ouverte.unige.ch/unige:42268

444 hits



Deposited on : 2014-11-28

Export document
Format :
Citation style :