title: Folding and organization of a contiguous chromosome region according to the gene distribution pattern in primary genomic sequence.
abstract: Specific mammalian genes functionally and dynamically associate together within the nucleus. Yet, how an array of many genes along the chromosome sequence can be spatially organized and folded together is unknown. We investigated the 3D structure of a well-annotated, highly conserved 4.3-Mb region on mouse chromosome 14 that contains four clusters of genes separated by gene "deserts." In nuclei, this region forms multiple, nonrandom "higher order" structures. These structures are based on the gene distribution pattern in primary sequence and are marked by preferential associations among multiple gene clusters. Associating gene clusters represent expressed chromatin, but their aggregation is not simply dependent on ongoing transcription. In chromosomes with aggregated gene clusters, gene deserts preferentially align with the nuclear periphery, providing evidence for chromosomal region architecture by specific associations with functional nuclear domains. Together, these data suggest dynamic, probabilistic 3D folding states for a contiguous megabase-scale chromosomal region, supporting the diverse activities of multiple genes and their conserved primary sequence organization.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Shopland
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Lynch
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Peterson
authors.forename: Kathleen
authors.initials: K
authors.lastname: Thornton
authors.forename: Nick
authors.initials: N
authors.lastname: Kepper
authors.forename: Johann von
authors.initials: Jv
authors.lastname: Hase
authors.forename: Stefan
authors.initials: S
authors.lastname: Stein
authors.forename: Sarah
authors.initials: S
authors.lastname: Vincent
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Molloy
authors.forename: Gregor
authors.initials: G
authors.lastname: Kreth
authors.forename: Christoph
authors.initials: C
authors.lastname: Cremer
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Bult
authors.forename: Timothy P
authors.initials: TP
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000737:chemistry* / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D016678:Genome; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells
chemical_list: D002843:Chromatin