title: Insulator function and topological domain border strength scale with architectural protein occupancy.
abstract: BACKGROUND
  Chromosome conformation capture studies suggest that eukaryotic genomes are organized into structures called topologically associating domains. The borders of these domains are highly enriched for architectural proteins with characterized roles in insulator function. However, a majority of architectural protein binding sites localize within topological domains, suggesting sites associated with domain borders represent a functionally different subclass of these regulatory elements. How topologically associating domains are established and what differentiates border-associated from non-border architectural protein binding sites remain unanswered questions.
  
  
  RESULTS
  By mapping the genome-wide target sites for several Drosophila architectural proteins, including previously uncharacterized profiles for TFIIIC and SMC-containing condensin complexes, we uncover an extensive pattern of colocalization in which architectural proteins establish dense clusters at the borders of topological domains. Reporter-based enhancer-blocking insulator activity as well as endogenous domain border strength scale with the occupancy level of architectural protein binding sites, suggesting co-binding by architectural proteins underlies the functional potential of these loci. Analyses in mouse and human stem cells suggest that clustering of architectural proteins is a general feature of genome organization, and conserved architectural protein binding sites may underlie the tissue-invariant nature of topologically associating domains observed in mammals.
  
  
  CONCLUSIONS
  We identify a spectrum of architectural protein occupancy that scales with the topological structure of chromosomes and the regulatory potential of these elements. Whereas high occupancy architectural protein binding sites associate with robust partitioning of topologically associating domains and robust insulator function, low occupancy sites appear reserved for gene-specific regulation within topological domains.
authors: Kevin
authors: K
authors: Van Bortle
authors: Michael H
authors: MH
authors: Nichols
authors: Li
authors: L
authors: Li
authors: Chin-Tong
authors: CT
authors: Ong
authors: Naomi
authors: N
authors: Takenaka
authors: Zhaohui S
authors: ZS
authors: Qin
authors: Victor G
authors: VG
authors: Corces
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002874:Chromosome Mapping; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics*; D017344:Genes, Insect; D006801:Humans; D020014:K562 Cells; D051379:Mice; D005810:Multigene Family; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics; D019474:Transcription Factors, TFIII / Q000502:physiology; D000097722:Cohesins; D000098832:Transcription Factor TFIIIC
chemical_list: D000251:Adenosine Triphosphatases; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D012097:Repressor Proteins; D019474:Transcription Factors, TFIII; D000097722:Cohesins; D000098832:Transcription Factor TFIIIC; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; C108312:condensin complexes