Epigenetics Podcast24 Aug 2023

Long-Range Transcriptional Control by 3D Chromosome Structure (Luca Giorgetti)

In this episode of the Epigenetics Podcast, we caught up with Luca Giorgetti from the Friedrich Miescher Institute to hear about his work on long-range transcriptional control by 3D chromosome structure.

Luca Giorgetti's research focuses on chromosomal interactions, transcriptional output, and the dynamics of enhancer-promoter relationships. His lab investigated the causal relationship between chromosome interactions and transcriptional events. They’ve found that by manipulating the contact probabilities between an enhancer and a promoter by changing their distance, these changes had a substantial effect on transcription levels. This project was an experiment that Luca Giorgetti was eager to do, and it allowed him to establish a smooth functional relationship between contact probabilities and changes in transcription levels.

References

Giorgetti, L., Galupa, R., Nora, E. P., Piolot, T., Lam, F., Dekker, J., Tiana, G., & Heard, E. (2014). Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription. Cell, 157(4), 950–963. https://doi.org/10.1016/j.cell.2014.03.025
Redolfi, J., Zhan, Y., Valdes-Quezada, C., Kryzhanovska, M., Guerreiro, I., Iesmantavicius, V., Pollex, T., Grand, R. S., Mulugeta, E., Kind, J., Tiana, G., Smallwood, S. A., de Laat, W., & Giorgetti, L. (2019). DamC reveals principles of chromatin folding in vivo without crosslinking and ligation. Nature structural & molecular biology, 26(6), 471–480. https://doi.org/10.1038/s41594-019-0231-0
Zuin, J., Roth, G., Zhan, Y., Cramard, J., Redolfi, J., Piskadlo, E., Mach, P., Kryzhanovska, M., Tihanyi, G., Kohler, H., Eder, M., Leemans, C., van Steensel, B., Meister, P., Smallwood, S., & Giorgetti, L. (2022). Nonlinear control of transcription through enhancer-promoter interactions. Nature, 604(7906), 571–577. https://doi.org/10.1038/s41586-022-04570-y
Mach, P., Kos, P. I., Zhan, Y., Cramard, J., Gaudin, S., Tünnermann, J., Marchi, E., Eglinger, J., Zuin, J., Kryzhanovska, M., Smallwood, S., Gelman, L., Roth, G., Nora, E. P., Tiana, G., & Giorgetti, L. (2022). Cohesin and CTCF control the dynamics of chromosome folding. Nature genetics, 54(12), 1907–1918. https://doi.org/10.1038/s41588-022-01232-7