Structural Variation-Associated Expression Changes Are Paralleled by Chromatin Architecture ModificationsReport as inadecuate




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Copy number variants CNVs influence the expression of genes that map not only within the rearrangement, but also to its flanks. To assess the possible mechanisms underlying this -neighboring effect-, we compared intrachromosomal interactions and histone modifications in cell lines of patients affected by genomic disorders and control individuals. Using chromosome conformation capture 4C-seq, we observed that a set of genes flanking the Williams-Beuren Syndrome critical region WBSCR were often looping together. The newly identified interacting genes include AUTS2, mutations of which are associated with autism and intellectual disabilities. Deletion of the WBSCR disrupts the expression of this group of flanking genes, as well as long-range interactions between them and the rearranged interval. We also pinpointed concomitant changes in histone modifications between samples.We conclude that large genomic rearrangements can lead to chromatin conformation changes that extend far away from the structural variant, thereby possibly modulating expression globally and modifying the phenotype.GEO Series accession number: GSE33784, GSE33867.



Author: Nele Gheldof , Robert M. Witwicki , Eugenia Migliavacca , Marion Leleu, Gérard Didelot, Louise Harewood, Jacques Rougemont, Alex

Source: http://plos.srce.hr/



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