Quantitative analysis of chromatin interaction changes upon a 4.3 Mb deletion at mouse 4E2

Cinthya J Zepeda-Mendoza, Swagatam Mukhopadhyay, Emily S Wong, Nathalie Harder, Erik Splinter, Elzo de Wit, Melanie A Eckersley-Maslin, Thomas Ried, Roland Eils, Karl Rohr, Alea Mills, Wouter de Laat, Paul Flicek, Anirvan M Sengupta, David L Spector

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)982
JournalBMC Genomics
Volume16
Issue number1
DOIs
Publication statusPublished - 2015

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