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Van Bortle, K., Nichols, M.H., Li, L., Ong, C.T., Takenaka, N., Qin, Z.S., Corces, V.G. (2014). Insulator function and topological domain border strength scale with architectural protein occupancy.  Genome Biol. 15(5): R82.
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Publication Type
Research paper

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. 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. 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.

PubMed ID
PubMed Central ID
PMC4226948 (PMC) (EuropePMC)
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    Parent Publication
    Publication Type
    Genome Biol.
    Genome Biology
    Publication Year
    1474-7596 1474-760X
    Data From Reference
    Genes (17)
    Physical Interactions (3)
    Cell Lines (2)