Understanding how the genome becomes spatially organized and folded inside the nucleus is central to understanding how chromosomes function in normal development and in disease. Recent advances have shown that nuclear organization is driven by a complex collection of chromosome interactions at different genomic scales, from small chromatin loops to larger intra- and inter-chromosomal interactions between well-demarcated chromatin domains. And yet, little is known about how chromosomal segments find each other and form stable interactions within cells.
We are using our custom Oligopaint FISH probes to identify signatures of chromosome arrangement across different cell cycle stages, tissues, and developmental time points in both Drosophila and mammalian cells. Our approach leverages the flexibility and scalability of Oligopaints to generate low-cost chromosome paints for systematic analyses of chromatin folding and positioning. Our experiments allow us to integrate levels of chromatin compaction, chromosome intermingling, and the epigenetic state of large domains in a single-cell and genome-wide manner. Using this approach, we are dissecting the contributions of putative architectural proteins to the radial positioning and folding of chromosomes as well as their function in genome integrity.