西亚试剂：Domains of genome-wide gene expressi0n dysregulation in Dow

Audrey Letourneau, Federico A. Santoni, Ximena Bonilla, M. Reza Sailani, David Gonzalez,Jop Kind, Claire Cheva1ier, Robert Thurman, Richard S. Sandstrom, Youssef Hibaoui,Marco Garieri, Konstantin Popadin, Emilie Falconnet, Maryline Gagnebin, Corinne Gehrig,Anne Vannier, Michel Guipponi, Laurent Farinelli, Daniel Robyr, Eugenia Migliavacca,Christelle Borel, Samuel Deutsch, Anis Feki, John A. Stamatoyannopoulos, Yann Heraultet al.

Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expressi0n in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcr-ptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expressi0n between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expressi0n dysregulation domains (GEDDs) can be defined by the expressi0n level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins’ fibroblasts. Comparison of the transcr-ptome 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 transcr-ptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.

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