title: Quantitative analysis of chromatin interaction changes upon a 4.3 Mb deletion at mouse 4E2.
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.
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA. czepedamendoza@bwh.harvard.edu.
authors.forename: Cinthya J
authors.initials: CJ
authors.lastname: Zepeda-Mendoza
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA. swagatam.mukhopadhyay@gmail.com.
authors.forename: Swagatam
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: The European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. em6@ebi.ac.uk.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Wong
authors.affiliation: Department Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, University of Heidelberg, BioQuant, IPMB, and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 267, 69120, Heidelberg, Germany. N.Harder@dkfz-heidelberg.de.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Harder
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584, CT Utrecht, The Netherlands. e.splinter@hubrecht.eu.
authors.forename: Erik
authors.initials: E
authors.lastname: Splinter
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584, CT Utrecht, The Netherlands. e.wit@hubrecht.eu.
authors.forename: Elzo
authors.initials: E
authors.lastname: de Wit
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA. eckersleymaslin@gmail.com.|Epigenetics Programme, Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK. eckersleymaslin@gmail.com.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Eckersley-Maslin
authors.affiliation: Center for Cancer Research, National Cancer Institute, National Institutes of Health, 50 South Drive, Bldg. 50, Rm. 1408, Bethesda, MD, 20892, USA. riedt@mail.nih.gov.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.affiliation: Department Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, University of Heidelberg, BioQuant, IPMB, and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 267, 69120, Heidelberg, Germany. r.eils@dkfz-heidelberg.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.affiliation: Department Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, University of Heidelberg, BioQuant, IPMB, and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 267, 69120, Heidelberg, Germany. k.rohr@dkfz.de.
authors.forename: Karl
authors.initials: K
authors.lastname: Rohr
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA. mills@cshl.edu.|Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA. mills@cshl.edu.
authors.forename: Alea
authors.initials: A
authors.lastname: Mills
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584, CT Utrecht, The Netherlands. w.laat@hubrecht.eu.
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
authors.affiliation: The European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. flicek@ebi.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.affiliation: Department of Physics and Astronomy, Rutgers, The State University of New Jersey, 136 Frelinghuysen Road, Piscataway, NJ, 08854-8019, USA. anirvan.m.sengupta@gmail.com.
authors.forename: Anirvan M
authors.initials: AM
authors.lastname: Sengupta
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA. spector@cshl.edu.|Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA. spector@cshl.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Spector
mesh_terms: D000483:Alleles; D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D033481:Chromosomes, Mammalian; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D015870:Gene Expression; D023281:Genomics / Q000379:methods; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D017384:Sequence Deletion
chemical_list: D002843:Chromatin