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In this episode of the Epigenetics Podcast, we talked with Alistair Boettiger from Stanford University about his work on the analysis of 3D chromatin structure of single cells using super-resolution imaging.\nAlistair Boettiger and his team focus on developing advanced microscopy techniques to understand gene regulation at the level of 3D genome organization. They have developed Optical Reconstruction of Chromatin Architecture (ORCA), a microscopy approach to trace the 3-dimensional DNA path in the nucleus with genomic resolution down to 2 kb and a throughput of ~10,000 cells per experiment. These methods enable the identification of structural features with comparable resolution to Hi-C, while the advantages of microscopy such as single cell resolution and multimodal measurements remain.\n\xa0\nReferences\n\nBoettiger, A., Bintu, B., Moffitt, J. et al. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529, 418\u2013422 (2016). https://doi.org/10.1038/nature16496\n\n\nBogdan Bintu et al., Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells. Science 362, eaau1783 (2018). DOI:10.1126/science.aau1783\n\n\nMateo, L.J., Sinnott-Armstrong, N. & Boettiger, A.N. Tracing DNA paths and RNA profiles in cultured cells and tissues with ORCA. Nat Protoc 16, 1647\u20131713 (2021). https://doi.org/10.1038/s41596-020-00478-x\n\n\nRajpurkar, A.R., Mateo, L.J., Murphy, S.E. et al. Deep learning connects DNA traces to transcription to reveal predictive features beyond enhancer\u2013promoter contact. Nat Commun 12, 3423 (2021). https://doi.org/10.1038/s41467-021-23831-4\n\n\nTzu-Chiao Hung, David M. Kingsley, & Alistair Boettiger. (2023). Boundary stacking interactions enable cross-TAD enhancer-promoter communication during limb development. BioRxiv, 2023.02.06.527380. https://doi.org/10.1101/2023.02.06.527380\n\n\nHafner, A., Park, M., Berger, S. E., Murphy, S. E., Nora, E. P., & Boettiger, A. N. (2023). Loop stacking organizes genome folding from TADs to chromosomes. Molecular cell, 83(9), 1377\u20131392.e6. https://doi.org/10.1016/j.molcel.2023.04.008\n\xa0\n\nRelated Episodes\n\nHi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)\n\n\nUnraveling Mechanisms of Chromosome Formation (Job Dekker)\n\n\nBiophysical Modeling of 3-D Genome Organization (Leonid Mirny)\n\n\xa0\n\nContact\n\nEpigenetics Podcast on Twitter\n\n\nEpigenetics Podcast on Instagram\n\n\nEpigenetics Podcast on Mastodon\n\n\nActive Motif on Twitter\n\n\nActive Motif on LinkedIn\n\n\nEmail: podcast@activemotif.com