title: Functional and topological characteristics of mammalian regulatory domains.
abstract: Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles.
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany;
authors.forename: Orsolya
authors.initials: O
authors.lastname: Symmons
authors.forename: Veli Vural
authors.initials: VV
authors.lastname: Uslu
authors.forename: Taro
authors.initials: T
authors.lastname: Tsujimura
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruf
authors.forename: Sonya
authors.initials: S
authors.lastname: Nassari
authors.forename: Wibke
authors.initials: W
authors.lastname: Schwarzer
authors.forename: Laurence
authors.initials: L
authors.lastname: Ettwiller
authors.forename: François
authors.initials: F
authors.lastname: Spitz
mesh_terms: D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic; D016678:Genome; D051379:Mice; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D012097:Repressor Proteins; D000097722:Cohesins; C000619698:Ctcf protein, mouse