Function of Insulators in 3D Genome Folding (Maria Gambetta)

Published: Nov. 16, 2023, 8:01 a.m.

b"In this episode of the Epigenetics Podcast, we talked with Maria Gambetta from the University of Lausanne about her work on the function of insulators in 3D genome folding.\\nMaria Gambetta focuses on investigating 3D contact dynamics between enhancers and promoters, providing insights into tissue-specific gene activation. The team used capture-C to analyze dynamic looping events, emphasizing the significance of accessible chromatin peaks in enhancer-promoter interactions. Furthermore, they focused on gene insulation and CTCF's role in forming topologically associating domains in Drosophila. Hi-C analysis on CTCF mutants revealed the conservation of TAD boundary mechanisms, identifying CP-190 as a potential binding protein.\\nTheir findings on the loss of TAD boundaries in mutants and the role of transcription in TAD boundary formation are discussed as well as the function of CP190 and insulators in preventing interactions between promoters and enhancers. Their work challenges existing models of insulator function and seeks to understand their mechanisms better. The conversation concludes with insights into long-range regulatory associations in Drosophila, emphasizing the punctual interactions between transcription factor binding sites and their effect on neural gene transcription and genome folding.\\n\\xa0\\nReferences\\n\\nGambetta, M. C., Oktaba, K., & M\\xfcller, J. (2009). Essential role of the glycosyltransferase sxc/Ogt in polycomb repression. Science (New York, N.Y.), 325(5936), 93\\u201396. https://doi.org/10.1126/science.1169727\\n\\n\\nKaushal, A., Mohana, G., Dorier, J., \\xd6zdemir, I., Omer, A., Cousin, P., Semenova, A., Taschner, M., Dergai, O., Marzetta, F., Iseli, C., Eliaz, Y., Weisz, D., Shamim, M. S., Guex, N., Lieberman Aiden, E., & Gambetta, M. C. (2021). CTCF loss has limited effects on global genome architecture in Drosophila despite critical regulatory functions. Nature communications, 12(1), 1011. https://doi.org/10.1038/s41467-021-21366-2\\n\\n\\nHoencamp, C., Dudchenko, O., Elbatsh, A. M. O., Brahmachari, S., Raaijmakers, J. A., van Schaik, T., Sede\\xf1o Cacciatore, \\xc1., Contessoto, V. G., van Heesbeen, R. G. H. P., van den Broek, B., Mhaskar, A. N., Teunissen, H., St Hilaire, B. G., Weisz, D., Omer, A. D., Pham, M., Colaric, Z., Yang, Z., Rao, S. S. P., Mitra, N., \\u2026 Rowland, B. D. (2021). 3D genomics across the tree of life reveals condensin II as a determinant of architecture type. Science (New York, N.Y.), 372(6545), 984\\u2013989. https://doi.org/10.1126/science.abe2218\\n\\n\\nMohana, G., Dorier, J., Li, X., Mouginot, M., Smith, R. C., Malek, H., Leleu, M., Rodriguez, D., Khadka, J., Rosa, P., Cousin, P., Iseli, C., Restrepo, S., Guex, N., McCabe, B. D., Jankowski, A., Levine, M. S., & Gambetta, M. C. (2023). Chromosome-level organization of the regulatory genome in the Drosophila nervous system. Cell, 186(18), 3826\\u20133844.e26. https://doi.org/10.1016/j.cell.2023.07.008\\n\\xa0\\n\\nRelated Episodes\\n\\nHi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)\\n\\n\\nBiophysical Modeling of 3-D Genome Organization (Leonid Mirny)\\n\\n\\nLong-Range Transcriptional Control by 3D Chromosome Structure (Luca Giorgetti)\\n\\n\\xa0\\nContact\\n\\nEpigenetics Podcast on Twitter/X\\n\\n\\nEpigenetics Podcast on Instagram\\n\\n\\nEpigenetics Podcast on Mastodon\\n\\n\\nEpigenetics Podcast on Bluesky\\n\\n\\nActive Motif on Twitter\\n\\n\\nActive Motif on LinkedIn\\n\\n\\nEmail: podcast@activemotif.com"