Melissa M. Harrison
Credentials: Transcriptional regulation during development
Position title: Professor
Phone: (608) 262-2382
6204B Biochemical Sciences Building
440 Henry Mall, Madison, WI 53706
• A.B. 1998, Harvard University
• Ph.D. 2006, M.I.T. (H.R. Horvitz)
• Postdoctoral Fellow 2006-2011, University of California, Berkeley (M.R. Botchan and T.W. Cline)
Honors & Awards
2014 Basil O’Connor Starter Scholar Research Award
2014 Wisconsin Partnership Program New Investigator Award
2016 Vallee Scholar Award
2017 American Cancer Society Research Scholar Award
2020 H.I. Romnes Award
2022 Invited plenary speaker, Annual Drosophila Research Conference
2022 Vilas Mid-Career Award
2023 Royal Society (UK) International Exchanges Award
Development and differentiation are driven by coordinated changes in gene expression. Early zygotic development is controlled by maternally contributed mRNAs and proteins, and transcriptional activation of the zygotic genome is delayed until hours after fertilization. This delayed transcriptional activation is a nearly universal phenomenon in all metazoans. Immediately following fertilization, the genome undergoes epigenetic reprogramming to allow for the transition from a specified germ cell to the pluripotent cells of the early embryo. The zygotic genome remains transcriptionally quiescent during these initial stages. Only at later cell cycles is widespread zygotic transcription initiated. This zygotic genome activation is tightly coordinated with the degradation of maternally provided mRNAs at the maternal-to-zygotic transition (MZT). Thus during this discrete developmental time point the transcriptional profile of the developing embryo undergoes a monumental reorganization.
While most of the genome is silenced prior to the MZT, a small subset of genes is expressed. These genes control fundamental processes essential for the future development of the organism and allow for progression through the MZT. Despite the fact that these developmental events are common from plants to vertebrates, little is currently known about the factors that regulate zygotic genome activation at the MZT or the mechanisms that allow for the selective transcription of a handful of genes at earlier time points. An understanding of these mechanisms will provide insights into how the genomes of pluripotent cells in general, including embryonic, cancer and induced-pluripotent stem cells, maintain their broad developmental potential while being poised to differentiate.
We use Drosophila melanogaster to study these phenomena using a wide variety of tools including biochemistry, genetics, molecular biology, genomics, and cell biology. Broadly, we are seeking to understand three outstanding questions: (1) why most of the genome is not transcribed until many nuclear divisions after fertilization, (2) how a small number of genes are expressed when the remainder of the genome is not, and (3) what triggers the widespread activation of the zygotic genome at the MZT.
Perform a customized PubMed literature search for Melissa M. Harrison
- Bulyk, M.L., J. Drouin, M.M. Harrison, J. Taipale, and K.S. Zaret. (2023). Pioneer factors - key regulators of chromatin and gene expression. Nature reviews. Genetics, .
- Gaskill, M.M., I.V. Soluri, A.E. Branks, A.P. Boka, M.R. Stadler, K. Vietor, H.S. Huang, T.J. Gibson, A. Mukherjee, M. Mir, S.A. Blythe, and M.M. Harrison. (2023). Localization of the Drosophila pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression. Developmental cell, 58: 1610-1624.e8.
- Harrison, M.M., A.J. Marsh, and C.A. Rushlow. (2023). Setting the stage for development: the maternal-to-zygotic transition in Drosophila. Genetics, .
- Theis, A., and M.M. Harrison. (2023). Reprogramming of three-dimensional chromatin organization in the early embryo. Current opinion in structural biology, 81: 102613.
- Rajan, A., L. Anhezini, N. Rives-Quinto, J.Y. Chhabra, M.C. Neville, E.D. Larson, S.F. Goodwin, M.M. Harrison, and C.Y. Lee. (2023). Low-level repressive histone marks fine-tune gene transcription in neural stem cells. eLife, 12: .
- Gibson, T.J., and M.M. Harrison. (2023). Protein-intrinsic properties and context-dependent effects regulate pioneer-factor binding and function. bioRxiv : the preprint server for biology, .
- Shirzadi, S., M. Asghari-Jafarabadi, M.M. Harrison, and H. Allahverdipour. (2022). Development and validation of the psychometric properties of the perceived barriers of mammography scale. Health care for women international, 1-21.
- Bellec, M., J. Dufourt, G. Hunt, H. Lenden-Hasse, A. Trullo, A. Zine El Aabidine, M. Lamarque, M.M. Gaskill, H. Faure-Gautron, M. Mannervik, M.M. Harrison, J.C. Andrau, C. Favard, O. Radulescu, and M. Lagha. (2022). The control of transcriptional memory by stable mitotic bookmarking. Nature communications, 13: 1176.
- Kapuria, S., H. Bai, J. Fierros, Y. Huang, F. Ma, T. Yoshida, A. Aguayo, F. Kok, K.M. Wiens, J.K. Yip, M.L. McCain, M. Pellegrini, M. Nagashima, P.F. Hitchcock, N. Mochizuki, N.D. Lawson, M.M.R. Harrison, and C.L. Lien. (2022). Heterogeneous pdgfrb+ cells regulate coronary vessel development and revascularization during heart regeneration. Development (Cambridge, England), 149: .
- Larson, E.D., H. Komori, T.J. Gibson, C.M. Ostgaard, D.C. Hamm, J.M. Schnell, C.Y. Lee, and M.M. Harrison. (2021). Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila. Nature communications, 12: 7153.