Melissa M. Harrison
Credentials: Transcriptional regulation during development
Position title: Associate 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
• Howard Hughes Predoctoral Fellow, 1999-2004
• American Cancer Society Postdoctoral Fellow, 2007-2010
• Wisconsin Partnership Program New Investigator Award 2014
• March of Dimes Basil O’Connor Starter Scholar Research Award 2014
• Vallee Foundation Young Investigator Award in Biomedical Science 2016
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
- 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.
- Larson, E.D., A.J. Marsh, and M.M. Harrison. (2021). Pioneering the developmental frontier. Molecular cell, 81: 1640-1650.
- Gaskill, M.M., T.J. Gibson, E.D. Larson, and M.M. Harrison. (2021). GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo. eLife, 10: .
- Jain, S.U., A.Q. Rashoff, S.D. Krabbenhoft, D. Hoelper, T.J. Do, T.J. Gibson, S.M. Lundgren, E.R. Bondra, S. Deshmukh, A.S. Harutyunyan, N. Juretic, N. Jabado, M.M. Harrison, and P.W. Lewis. (2020). H3 K27M and EZHIP Impede H3K27-Methylation Spreading by Inhibiting Allosterically Stimulated PRC2. Molecular cell, 80: 726-735.e7.
- Nevil, M., T.J. Gibson, C. Bartolutti, A. Iyengar, and M.M. Harrison. (2020). Establishment of chromatin accessibility by the conserved transcription factor Grainy head is developmentally regulated. Development (Cambridge, England), 147: .
- McDaniel, S.L., A.J. Hollatz, A.M. Branstad, M.M. Gaskill, C.A. Fox, and M.M. Harrison. (2020). Tissue-Specific DNA Replication Defects in Drosophila melanogaster Caused by a Meier-Gorlin Syndrome Mutation in Orc4. Genetics, 214: 355-367.
- Tohidi, M., S.B. Brogly, K. Lajkosz, M.M. Harrison, A.R. Campbell, E. VanDenKerkhof, and S.M. Mann. (2019). Ten-year risk of complication and mortality after total hip arthroplasty in morbidly obese patients: a population study Canadian journal of surgery. Journal canadien de chirurgie, 62: 442-449.
- Fernandez Garcia, M., C.D. Moore, K.N. Schulz, O. Alberto, G. Donague, M.M. Harrison, H. Zhu, and K.S. Zaret. (2019). Structural Features of Transcription Factors Associating with Nucleosome Binding. Molecular cell, 75: 921-932.e6.
- McDaniel, S.L., and M.M. Harrison. (2019). Optogenetic Inactivation of Transcription Factors in the Early Embryo of Drosophila. Bio-protocol, 9: e3296.
- Reese, R.M., M.M. Harrison, and E.T. Alarid. (2019). Grainyhead-like Protein 2: The Emerging Role in Hormone-Dependent Cancers and Epigenetics. Endocrinology, 160: 1275-1288.