Illuminating genome organization through integrated microscopy and sequencing
In the nucleus of eukaryotic cells, a significant portion of the genome consists of lamina-associated domains, which are preferentially located at the nuclear periphery. However, how the remaining parts of the genome are exactly radially organized in the nucleus remains largely unknown. During my lecture I will describe a method named Genomic loci Positioning by Sequencing (GPSeq), which allows for genome-wide measurements of the distance to the nuclear lamina. Using GPSeq, we generated reproducible maps of the radial organization of the genome in human cells, at various resolutions, that revealed radial gradients of genomic and epigenomic features, gene expression, as well as A/B compartments and chromatin loops. We assessed the contribution of various features in predicting radiality, and found GC-content to have the strongest predictive power at all resolutions. Finally, we show that, by combining GPSeq radial information with Hi-C intra- and trans-chromosomal contacts, we are able to build whole-genome structure predictions much more accurately than possible thus far. Our data demonstrate that GPSeq is a powerful method to study genome architecture and reveal that the cell nucleus has a much finer level of radial organization than previously appreciated.