In this episode of the Epigenetics Podcast, we caught up with Melissa Harrison from the University of Wisconsin-Madison to talk about her work on the “Pioneer” Transcription Factors - Zelda and Grainyhead - and their role at the maternal-to-zygotic transition.
The Harrison lab studies how differentiation and development are driven by coordinated changes in gene expression. To do this, the targets of choice are the transcription factors Zelda and Grainyhead that bind to the genome at specific and crucial points in development and differentiation. These specialised transcription factors have the ability to bind to DNA in the context of nucleosomes which defines regulatory elements and leads to subsequent binding of additional classical transcription factors. These properties allow pioneer factors to act at the top of gene regulatory networks and control developmental transitions.
 
References

Harrison, M. M., Botchan, M. R., & Cline, T. W. (2010). Grainyhead and Zelda compete for binding to the promoters of the earliest-expressed Drosophila genes. Developmental biology, 345(2), 248–255. https://doi.org/10.1016/j.ydbio.2010.06.026


Harrison, M. M., Li, X. Y., Kaplan, T., Botchan, M. R., & Eisen, M. B. (2011). Zelda binding in the early Drosophila melanogaster embryo marks regions subsequently activated at the maternal-to-zygotic transition. PLoS genetics, 7(10), e1002266. https://doi.org/10.1371/journal.pgen.1002266


McDaniel, S. L., Gibson, T. J., Schulz, K. N., Fernandez Garcia, M., Nevil, M., Jain, S. U., Lewis, P. W., Zaret, K. S., & Harrison, M. M. (2019). Continued Activity of the Pioneer Factor Zelda Is Required to Drive Zygotic Genome Activation. Molecular cell, 74(1), 185–195.e4. https://doi.org/10.1016/j.molcel.2019.01.014


McDaniel, S. L., & Harrison, M. M. (2019). Optogenetic Inactivation of Transcription Factors in the Early Embryo of Drosophila. Bio-protocol, 9(13), e3296. https://doi.org/10.21769/BioProtoc.3296


Larson, E.D., Komori, H., Gibson, T.J. et al. Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila. Nat Commun 12, 7153 (2021). https://doi.org/10.1038/s41467-021-27506-y
 


Related Episodes

Pioneer Transcription Factors and Their Influence on Chromatin Structure (Ken Zaret)


 
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