title: The detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genomes.
abstract: BACKGROUND
  The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function-the storage, expression, and replication of genetic information-is still one of the central issues in biology. Here, we describe the much debated 3D architecture of the human and mouse genomes from the nucleosomal to the megabase pair level by a novel approach combining selective high-throughput high-resolution chromosomal interaction capture (T2C), polymer simulations, and scaling analysis of the 3D architecture and the DNA sequence.
  
  
  RESULTS
  The genome is compacted into a chromatin quasi-fibre with ~5 ± 1 nucleosomes/11 nm, folded into stable ~30-100 kbp loops forming stable loop aggregates/rosettes connected by similar sized linkers. Minor but significant variations in the architecture are seen between cell types and functional states. The architecture and the DNA sequence show very similar fine-structured multi-scaling behaviour confirming their co-evolution and the above.
  
  
  CONCLUSIONS
  This architecture, its dynamics, and accessibility, balance stability and flexibility ensuring genome integrity and variation enabling gene expression/regulation by self-organization of (in)active units already in proximity. Our results agree with the heuristics of the field and allow "architectural sequencing" at a genome mechanics level to understand the inseparable systems genomic properties.
authors.affiliation: Biophysical Genomics, Department of Cell Biology and Genetics, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. TA.Knoch@taknoch.org.
authors.forename: Tobias A
authors.identifier: http://orcid.org/0000-0002-6289-0315
authors.initials: TA
authors.lastname: Knoch
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstr. 1, 69117, Heidelberg, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Wachsmuth
authors.affiliation: Biophysical Genomics, Department of Cell Biology and Genetics, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.|Genome Organization and Function, BioQuant and German Cancer Research Center, Im Neuenheimer Feld 267, 69120, Heidelberg, Germany.
authors.forename: Nick
authors.initials: N
authors.lastname: Kepper
authors.affiliation: Biophysical Genomics, Department of Cell Biology and Genetics, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Lesnussa
authors.affiliation: Biophysical Genomics, Department of Cell Biology and Genetics, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Anis
authors.initials: A
authors.lastname: Abuseiris
authors.affiliation: Biophysical Genomics, Department of Cell Biology and Genetics, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.|Cell Biology, Department Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Ali Imam
authors.affiliation: Biophysical Genomics, Department of Cell Biology and Genetics, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.|Cell Biology, Department Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Petros
authors.initials: P
authors.lastname: Kolovos
authors.affiliation: Cohesin in Chromatin Structure and Gene Regulation, Department of Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Jessica
authors.initials: J
authors.lastname: Zuin
authors.affiliation: Center for Biomics, Department of Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Christel E M
authors.initials: CEM
authors.lastname: Kockx
authors.affiliation: Center for Biomics, Department of Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Rutger W W
authors.initials: RWW
authors.lastname: Brouwer
authors.affiliation: Cell Biology, Department Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Harmen J G
authors.initials: HJG
authors.lastname: van de Werken
authors.affiliation: Center for Biomics, Department of Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Wilfred F J
authors.initials: WFJ
authors.lastname: van IJcken
authors.affiliation: Cohesin in Chromatin Structure and Gene Regulation, Department of Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Kerstin S
authors.initials: KS
authors.lastname: Wendt
authors.affiliation: Cell Biology, Department Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Grosveld
keywords: Cell nucleus architecture; Chromatin fibre; Chromatin loops; Chromatin rosettes; DNA sequence organization; Genome organization; Nucleosome; Polymer physics simulation; Targeted chromatin capture