title: Segmental folding of chromosomes: a basis for structural and regulatory chromosomal neighborhoods?
abstract: We discuss here a series of testable hypotheses concerning the role of chromosome folding into topologically associating domains (TADs). Several lines of evidence suggest that segmental packaging of chromosomal neighborhoods may underlie features of chromatin that span large domains, such as heterochromatin blocks, association with the nuclear lamina and replication timing. By defining which DNA elements preferentially contact each other, the segmentation of chromosomes into TADs may also underlie many properties of long-range transcriptional regulation. Several observations suggest that TADs can indeed provide a structural basis to regulatory landscapes, by controlling enhancer sharing and allocation. We also discuss how TADs may shape the evolution of chromosomes, by causing maintenance of synteny over large chromosomal segments. Finally we suggest a series of experiments to challenge these ideas and provide concrete examples illustrating how they could be practically applied.
authors.affiliation: Institut Curie, Paris, France. elphege.nora@gladstone.ucsf.edu
authors.forename: Elphège P
authors.initials: EP
authors.lastname: Nora
authors.forename: Job
authors.initials: J
authors.lastname: Dekker
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics*; D004247:DNA / Q000235:genetics; D042522:DNA Replication Timing; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D004247:DNA
keywords: chromatin domains; chromatin folding; chromosome conformation capture (3C); long-range transcriptional regulation; regulatory landscapes; topologically associating chromosome domains