Ultra-long-range interactions between active regulatory elements.

Autor:	Friman ET; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom; Elias.Friman@ed.ac.uk Wendy.Bickmore@ed.ac.uk., Flyamer IM; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom., Marenduzzo D; School of Physics and Astronomy, University of Edinburgh, Edinburgh EH9 3FD, United Kingdom., Boyle S; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom., Bickmore WA; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom; Elias.Friman@ed.ac.uk Wendy.Bickmore@ed.ac.uk.
Jazyk:	angličtina
Zdroj:	Genome research [Genome Res] 2023 Aug; Vol. 33 (8), pp. 1269-1283. Date of Electronic Publication: 2023 Jul 14.
DOI:	10.1101/gr.277567.122
Abstrakt:	Contacts between enhancers and promoters are thought to relate to their ability to activate transcription. Investigating factors that contribute to such chromatin interactions is therefore important for understanding gene regulation. Here, we have determined contact frequencies between millions of pairs of cis -regulatory elements from chromosome conformation capture data sets and analyzed a collection of hundreds of DNA-binding factors for binding at regions of enriched contacts. This analysis revealed enriched contacts at sites bound by many factors associated with active transcription. We show that active regulatory elements, independent of cohesin and polycomb, interact with each other across distances of tens of megabases in vertebrate and invertebrate genomes and that interactions correlate and change with activity. However, these ultra-long-range interactions are not dependent on RNA polymerase II transcription or individual transcription cofactors. Using simulations, we show that a model of chromatin and multivalent binding factors can give rise to long-range interactions via bridging-induced clustering. We propose that long-range interactions between cis -regulatory elements are driven by at least three distinct processes: cohesin-mediated loop extrusion, polycomb contacts, and clustering of active regions. (© 2023 Friman et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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