2011/03/15 by Swagatam Mukhopadhyay, Paul Schedl, Paul D. Schedl +2 · 34 citations
Biochemistry, Genetics and Molecular Biology · #Action (physics) #Biology #Chromatin #Computational biology #DNA #Enhancer #Gene #Genetics #Genomics and Chromatin Dynamics #Materials science #Physics #Protein Degradation and Inhibitors #Quantum mechanics #RNA Research and Splicing #Range (aeronautics) #Transcription factor #q-bio.SC
paper · pdf · doi:10.1073/pnas.1103845108
published in Proceedings of the National Academy of Sciences 108(50), 19919-19924 (National Academy of Sciences) · 10 pages, originally submitted to an (undisclosed) journal in May 2010
arxiv created 2011/03/15 · openalex publication_date 2011/11/28 · arxiv updated 2015/05/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
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.