In this episode of the Epigenetics Podcast, we talked with Kyle Eagen from Baylor College of Medicine about his work on BET Proteins and their role in chromosome folding and compartmentalization.

In the early days of his research career Dr. Eagen made use of genomics and microscopy to study chromosomes, particularly polytene chromosomes in Drosophila. The correlation between the folding patterns detected by Hi-C and polytene bands highlights the similarities between the two, bridging traditional cytology with modern NGS methods. This work formed the basis of Kyle's thesis and sparked his interest in nuclear organization and chromosome 3D structure.

In his independent lab Kyle then studied compartments in chromatin structure and focused on the relationship between histone modifications and the 3D structure of chromosomes. The discovery of BRD4-NUT, a fusion oncoprotein that reprograms chromosome 3D structure, is highlighted as a significant step forward in understanding chromatin structure.

The conversation then shifts to the use of a tool to test hypotheses about the involvement of BRD4 in a specific process, leading to consistent results and considerations for manipulating chromosome organization for therapeutic purposes. The role of BET proteins in genome folding and the need for further research on other factors involved in 3D genome structure are discussed.

Rosencrance, C. D., Ammouri, H. N., Yu, Q., Ge, T., Rendleman, E. J., Marshall, S. A., & Eagen, K. P. (2020). Chromatin Hyperacetylation Impacts Chromosome Folding by Forming a Nuclear Subcompartment. Molecular Cell, 78(1), 112-126.e12. https://doi.org/10.1016/j.molcel.2020.03.018

Huang, Y., Durall, R. T., Luong, N. M., Hertzler, H. J., Huang, J., Gokhale, P. C., Leeper, B. A., Persky, N. S., Root, D. E., Anekal, P. V., Montero Llopis, P. D. L. M., David, C. N., Kutok, J. L., Raimondi, A., Saluja, K., Luo, J., Zahnow, C. A., Adane, B., Stegmaier, K., … French, C. A. (2023). EZH2 Cooperates with BRD4-NUT to Drive NUT Carcinoma Growth by Silencing Key Tumor Suppressor Genes. Cancer Research, 83(23), 3956–3973. https://doi.org/10.1158/0008-5472.CAN-23-1475

Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)

Genome Organization Mediated by RNA Polymerase II (Argyrys Papantonis)

Analysis of 3D Chromatin Structure Using Super-Resolution Imaging (Alistair Boettiger)

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