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.
Alistair 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.
References
Boettiger, A., Bintu, B., Moffitt, J. et al. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529, 418–422 (2016). https://doi.org/10.1038/nature16496
Bogdan Bintu et al., Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells. Science 362, eaau1783 (2018). DOI:10.1126/science.aau1783
Mateo, L.J., Sinnott-Armstrong, N. & Boettiger, A.N. Tracing DNA paths and RNA profiles in cultured cells and tissues with ORCA. Nat Protoc 16, 1647–1713 (2021). https://doi.org/10.1038/s41596-020-00478-x
Rajpurkar, A.R., Mateo, L.J., Murphy, S.E. et al. Deep learning connects DNA traces to transcription to reveal predictive features beyond enhancer–promoter contact. Nat Commun 12, 3423 (2021). https://doi.org/10.1038/s41467-021-23831-4
Tzu-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
Hafner, 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), 1377–1392.e6. https://doi.org/10.1016/j.molcel.2023.04.008
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Effects of DNA Methylation on Chromatin Structure and Transcription (Dirk Schübeler)
CpG Islands, DNA Methylation, and Disease (Adrian Bird)
Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)
From Nucleosome Structure to Function (Karolin Luger)
Identification of Functional Elements in the Genome (Bing Ren)
Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)
Chromatin Structure and Dynamics at Ribosomal RNA Genes (Tom Moss)
Epigenetic Origins Of Heterogeneity And Disease (Andrew Pospisilik)
PIXUL: On the Leading Edge of Chromatin Shearing (Karol Bomsztyk and Tom Matula)
Influence of Histone Variants on Chromatin Structure and Metabolism (Markus Buschbeck)
Epigenetic Mechanisms of Aging and Longevity (Shelley Berger)
Epigenetics & Glioblastoma: New Approaches to Treat Brain Cancer (Lucy Stead)
The Past, Present, and Future of Epigenetics (Joe Fernandez, founder of Active Motif)
The Interchromatin Network Model (Ana Pombo)
Dosage Compensation in Drosophila (Asifa Akhtar)
Spatial Organization of the Human Genome (Wendy Bickmore)
Heterochromatin and Phase Separation (Gary Karpen)
Diabetes and Epigenetics (Jean-Sébastien Annicotte)
Epigenetics and X-inactivation (Edith Heard)
Chromatin Organization (Susan Gasser)
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