Theoretical analysis of the role of chromatin interactions in long-range action of enhancers and insulators

Swagatam Mukhopadhyay, Paul Schedl, Vasily M. Studitsky, Anirvan M. Sengupta

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Long-distance regulatory interactions between enhancers and their target genes are commonplace in higher eukaryotes. Interposed boundaries or insulators are able to block these long-distance regulatory interactions. The mechanistic basis for insulator activity and how it relates to enhancer action-at-a-distance remains unclear. Here we explore the idea that topological loops could simultaneously account for regulatory interactions of distal enhancers and the insulating activity of boundary elements. We show that while loop formation is not in itself sufficient to explain action at a distance, incorporating transient nonspecific and moderate attractive interactions between the chromatin fibers strongly enhances long-distance regulatory interactions and is sufficient to generate a euchromatin-like state. Under these same conditions, the subdivision of the loop into two topologically independent loops by insulators inhibits interdomain interactions. The underlying cause of this effect is a suppression of crossings in the contact map at intermediate distances. Thus our model simultaneously accounts for regulatory interactions at a distance and the insulator activity of boundary elements. This unified model of the regulatory roles of chromatin loops makes several testable predictions that could be confronted with in vitro experiments, as well as genomic chromatin conformation capture and fluorescent microscopic approaches.

Original languageEnglish (US)
Pages (from-to)19919-19924
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - Dec 13 2011

All Science Journal Classification (ASJC) codes

  • General


  • Chromatin-polymer model
  • Enhancer-promoter
  • Long-range gene regulation


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