Genomics

Dataset Information

239

Domains of genomewide gene expression dysregulation in Down syndrome [ChIP-seq]


ABSTRACT: Trisomy 21 (T21) is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in T21, and to eliminate the noise of the genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for T21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either up- 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 DS and wild-type, 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 LADs position was not altered in trisomic cells. However, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results suggest 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 T21 phenotypes. H3K4me3 ChIP-Seq profiling of monozygotic twins discordant for trisomy 21.

ORGANISM(S): Homo sapiens  

SUBMITTER: Youssef Hibaoui   John A Stamatoyannopoulos  Corinne Gehrig  Ximena Bonilla  Richard S Sandstrom  Michel Guipponi  Bas van Steensel  Federico A Santoni  Laurent Farinelli  Robert Thurman  Emilie Falconnet  M.Reza Sailani  David Gonzalez  Daniel Robyr  Konstantin Popadin  Audrey Letourneau  Samuel Deutsch  Yann Herault  Maryline Gagnebin  Marco Garieri  Stylianos E Antonarakis  Anis Feki  Roderic Guigo  Christelle Borel  Jop Kind  Anne Vannier  Eugenia Migliavacca  Claire Chevalier 

PROVIDER: E-GEOD-55506 | ArrayExpress | 2014-04-08

SECONDARY ACCESSION(S): GSE55506SRP039363PRJNA239812

REPOSITORIES: GEO, ArrayExpress, ENA

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