Quantitative analysis of chromatin interaction changes upon a 4.3 Mb deletion at mouse 4E2. (December 2015)

• Record Type: Journal Article
• Authors: Zepeda-Mendoza, Cinthya; Mukhopadhyay, Swagatam; Wong, Emily; Harder, Nathalie; Splinter, Erik; de Wit, Elzo; Eckersley-Maslin, Melanie; Ried, Thomas; Eils, Roland; Rohr, Karl; Mills, Alea; de Laat, Wouter; Flicek, Paul; Sengupta, Anirvan; Spector, David
• Is Part Of: BMC genomics. Volume 16:Number 1(2015)
• Page Start: 1
• Page End: 17
• Publication Date: 2015-12
• Subjects: Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/s12864-015-2137-5
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Background Circular chromosome conformation capture (4C) has provided important insights into three dimensional (3D) genome organization and its critical impact on the regulation of gene expression. We developed a new quantitative framework based on polymer physics for the analysis of paired-end sequencing 4C (PE-4Cseq) data. We applied this strategy to the study of chromatin interaction changes upon a 4.3 Mb DNA deletion in mouse region 4E2. Results A significant number of differentially interacting regions (DIRs) and chromatin compaction changes were detected in the deletion chromosome compared to a wild-type (WT) control. Selected DIRs were validated by 3D DNA FISH experiments, demonstrating the robustness of our pipeline. Interestingly, significant overlaps of DIRs with CTCF/Smc1 binding sites and differentially expressed genes were observed. Conclusions Altogether, our PE-4Cseq analysis pipeline provides a comprehensive characterization of DNA deletion effects on chromatin structure and function.