Our approach leverages the flexibility and scalability of Oligopaints to generate low-cost chromosome paints for systematic analyses of chromatin folding and positioning. Typically, studies of chromosome positioning have been stymied by the lack of affordable, high-resolution FISH probes, which are usually targeted to only a few loci at a time. Moreover, not only are conventional technologies not a practical source of probe for use in high-throughput methodologies, they fall short of revealing the location of whole chromosomes or specific sub-chromosomal regions in interphase nuclei. In contrast to conventional approaches, Oligopaints are computationally designed, synthesized on microarrays, and generated via PCR amplification. This strategy provides precise control over the sequences they target and allows for multicolor imaging of regions ranging from a few Kb to whole chromosomes with the same basic protocol. Our previous work generated Oligopaints to the entire unique portion of the Drosophila genome in a chromosome arm-specific manner, enhancing our ability to measure large-scale chromatin folding. More recently, we have also synthesized Oligopaints to three entire human chromosomes – chr18, 19, and 22 – in an effort to paint the entire the human genome. These paints are renewable, cost-effective, and versatile as they can be amplified to specifically label different 3D chromatin features (TADs, compartments, etc.).
Please contact us if you would like to contribute to this effort by nominating (and paying for) the synthesis of additional chromosomes.