Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)

In this episode of the Epigenetics Podcast, we caught up with Diane Dickel from Lawrence Berkeley National Laboratory to talk about her work on ultraconserved enhancers and enhancer redundancy.

Diane Dickel and her co-workers study non-coding regions of the genome that harbor distant-acting transcriptional regulatory regions, called enhancers. Enhancers have been shown to be critical for normal embryonic development, implying evolutional conservation. Diane Dickel and her team try to identify and characterize enhancers at a genomic scale. Their efforts include the use of CRISPR/CAS9 to mutate enhancer sequences in order to understand sequence dependent functional relevance.

In this episode we discuss the function of ultraconserved enhancers, what ultraconservation actually means, how enhancer redundancy works and how Diane Dickel dealt with a failed PhD project.

References

• Dickel, D. E., Ypsilanti, A. R., Pla, R., Zhu, Y., Barozzi, I., Mannion, B. J., Khin, Y. S., Fukuda-Yuzawa, Y., Plajzer-Frick, I., Pickle, C. S., Lee, E. A., Harrington, A. N., Pham, Q. T., Garvin, T. H., Kato, M., Osterwalder, M., Akiyama, J. A., Afzal, V., Rubenstein, J. L. R., … Visel, A. (2018). Ultraconserved Enhancers Are Required for Normal Development. Cell, 172(3), 491-499.e15. https://doi.org/10.1016/j.cell.2017.12.017

• Gorkin, D. U., Barozzi, I., Zhao, Y., Zhang, Y., Huang, H., Lee, A. Y., Li, B., Chiou, J., Wildberg, A., Ding, B., Zhang, B., Wang, M., Strattan, J. S., Davidson, J. M., Qiu, Y., Afzal, V., Akiyama, J. A., Plajzer-Frick, I., Novak, C. S., … Ren, B. (2020). An atlas of dynamic chromatin landscapes in mouse fetal development. Nature, 583(7818), 744–751. https://doi.org/10.1038/s41586-020-2093-3

• Snetkova, V., Ypsilanti, A. R., Akiyama, J. A., Mannion, B. J., Plajzer-Frick, I., Novak, C. S., Harrington, A. N., Pham, Q. T., Kato, M., Zhu, Y., Godoy, J., Meky, E., Hunter, R. D., Shi, M., Kvon, E. Z., Afzal, V., Tran, S., Rubenstein, J. L. R., Visel, A., … Dickel, D. E. (2021). Ultraconserved enhancer function does not require perfect sequence conservation. Nature Genetics, 53(4), 521–528. https://doi.org/10.1038/s41588-021-00812-3

Related Episodes

• Identification of Functional Elements in the Genome (Bing Ren)

• Epigenetic Reprogramming During Mammalian Development (Wolf Reik)

• Unraveling Mechanisms of Chromosome Formation (Job Dekker)

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