Mukhopadhyay, S., Schedl, P., Studitsky, V. M., Sengupta, A. M. (December 2011) Theoretical analysis of the role of chromatin interactions in long-range action of enhancers and insulators. Proceedings of the National Academy of Sciences of the United States of America, 108 (50). pp. 19919-19924. ISSN 0027-8424
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Abstract
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | chromatin-polymer model enhancer-promoter long-range gene regulation histone tail domains interactions in-vivo interphase chromosomes nuclear-organization compaction drosophila transcription distance fiber dna |
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes |
| CSHL Authors: | |
| Communities: | CSHL labs > Wigler lab |
| Depositing User: | Matt Covey |
| Date: | December 2011 |
| Date Deposited: | 06 Feb 2013 19:17 |
| Last Modified: | 02 Jan 2018 21:13 |
| PMCID: | PMC3250180 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27179 |
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