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Peter Meister

Multi-contact chromosome conformation capture using nanopore sequencing in nematodes

About Peter Meister

Peter Meister completed his PhD in Molecular and Cellular Genetics at Institut Curie/University of Paris before completing a post-doc at the Friedrich Miescher Institute in Basel. Since 2011 he has been group leader of the Cell Fate and Nuclear Organization Laboratory at University of Bern.

Abstract

A wealth of studies has shown that gene regulation occurs at different scales, ranging from the promoter to the localization of the gene inside the nuclear space. Our laboratory studies dosage compensation in the nematode C. elegans, in which a condensin-like complex modifies the three-dimensional folding and position of the X chromosome, and down-regulates expression of X-linked genes. To understand how chromosome folding impacts gene expression, we use chromosome conformation capture (3C) technologies. For 3C, chromatin is cross-linked before DNA is digested in situ by a restriction enzyme. The restriction fragments are then ligated together, leading to formation of “contact” molecules in which fragments distant on the linear genome are ligated together. The 3D proximity of fragments makes them more likely to get ligated. One of the main limitations of 3C is the fact that each end of restriction fragments can be ligated only once, meaning that one can only identify pair-wise interactions and multi-way interactions can only be inferred from contact frequencies averaged over many cells. To overcome this limitation and to characterize gene conformation in single cells, we use nanopore long-read sequencing, thereby capturing many contacts per sequenced molecule. Initial results using this technology will be presented.

Peter Meister

Peter Meister

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