Insulator function and topological domain border strength scale with architectural protein occupancy

Genome Biology
Kevin Van BortleVictor G Corces

Abstract

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 ...Continue Reading

Citations

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Datasets Mentioned

BETA
GSE32970
GSE29218
GSE51816
E-MTAB-767
-220
-90
GSE31477
GSE54529

Methods Mentioned

BETA
transgenic
ChIP-seq
ChIP-chip
immunoprecipitation
Hi-C
Hi-C.
ChIP
ChIP-exo

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