Evolutionary Forces Shaping Mammalian Gene Regulation (Emily Wong)

In this episode of the Epigenetics Podcast, we talked with Emily Wong from the University of New South Wales in Sydney about her work on how evolution shapes mammalian genes.

As the head of the Regulatory Systems Lab at the Victor Chang Cardiac Research Institute and an associate professor at UNSW, Emily’s research centers on gene control and enhancers. We delve into her pivotal 2017 publication in Nature Communications, where she investigated transcription factor binding in liver-specific contexts, shedding light on the regulatory mechanisms at play in mammals.

Emily elaborates on her postdoctoral work at the European Bioinformatics Institute and the innovative hybrid systems she used to dissect genetic variation effects, which allowed her to differentiate between cis-regulatory and trans-regulatory influences. By employing techniques like ChIP-seq, she was able to illustrate the combinatorial effects of transcription factors on gene expression, paving the way for her collaborative efforts across disciplines and organisms.

We also examine Emily's findings regarding enhancer function through comparative studies between zebrafish and marine sponges. Using historical data on conserved genetic sequences, she and her team identified enhancer regions that displayed activity in specific vertebrate cell types, despite their evolutionary divergence from sponges. This unexpected result suggests deeper insights into how enhancers can be co-opted for new functions as species evolve.

Furthermore, we dive into Emily's latest ventures involving advanced methodologies such as chromatin accessibility profiling with ATAC-seq and how these insights can elucidate the genomic landscape of metazoan embryogenesis. She highlights significant correlations between enhancer turnover and DNA replication timing, suggesting evolutionary implications that should be taken into account in future genomic studies.

References

• Wong, E. S., Zheng, D., Tan, S. Z., Bower, N. I., Garside, V., Vanwalleghem, G., Gaiti, F., Scott, E., Hogan, B. M., Kikuchi, K., McGlinn, E., Francois, M., & Degnan, B. M. (2020). Deep conservation of the enhancer regulatory code in animals. Science, 370(6517), eaax8137. https://doi.org/10.1126/science.aax8137

• Cornejo-Páramo, P., Petrova, V., Zhang, X. et al. Emergence of enhancers at late DNA replicating regions. Nat Commun 15, 3451 (2024). https://doi.org/10.1038/s41467-024-47391-5

Related Episodes

• Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)

• Enhancer Communities in Adipocyte Differentiation (Susanne Mandrup)

• Enhancer-Promoter Interactions During Development (Yad Ghavi-Helm)

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