title: Architectural protein subclasses shape 3D organization of genomes during lineage commitment.
abstract: Understanding the topological configurations of chromatin may reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here, we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3D interactions that undergo marked reorganization at the submegabase scale during differentiation. Distinct combinations of CCCTC-binding factor (CTCF), Mediator, and cohesin show widespread enrichment in chromatin interactions at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant subdomains. Conversely, Mediator/cohesin bridge short-range enhancer-promoter interactions within and between larger subdomains. Knockdown of Smc1 or Med12 in embryonic stem cells results in disruption of spatial architecture and downregulation of genes found in cohesin-mediated interactions. We conclude that cell-type-specific chromatin organization occurs at the submegabase scale and that architectural proteins shape the genome in hierarchical length scales.
authors.affiliation: Department of Biology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Phillips-Cremins
authors.forename: Michael E G
authors.initials: ME
authors.lastname: Sauria
authors.forename: Amartya
authors.initials: A
authors.lastname: Sanyal
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Gerasimova
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Lajoie
authors.forename: Joshua S K
authors.initials: JS
authors.lastname: Bell
authors.forename: Chin-Tong
authors.initials: CT
authors.lastname: Ong
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Hookway
authors.forename: Changying
authors.initials: C
authors.lastname: Guo
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Sun
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bland
authors.forename: William
authors.initials: W
authors.lastname: Wagstaff
authors.forename: Stephen
authors.initials: S
authors.lastname: Dalton
authors.forename: Todd C
authors.initials: TC
authors.lastname: McDevitt
authors.forename: Ranjan
authors.initials: R
authors.lastname: Sen
authors.forename: Job
authors.initials: J
authors.lastname: Dekker
authors.forename: James
authors.initials: J
authors.lastname: Taylor
authors.forename: Victor G
authors.initials: VG
authors.lastname: Corces
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism; D019070:Cell Lineage; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000737:chemistry / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D016678:Genome; D055106:Genome-Wide Association Study; D056892:Mediator Complex / Q000235:genetics / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D056892:Mediator Complex; D009687:Nuclear Proteins; D012097:Repressor Proteins; D000097722:Cohesins; C000619698:Ctcf protein, mouse