Pioneers, settlers and life on the OregonR trail: transcriptional regulation during development

Melissa Harrison, PhD
Professor
Department of Biomolecular Chemistry
University of Wisconsin-Madison
School of Medicine and Public Health
Madison, WI, USA

This conference is hosted by Jacques Drouin, PhD. This conference is part of the 2024-2025 IRCM conference calendar.

About this conference
The DNA genome is differentially interpreted over development, ensuring expression of genes where and when they are needed. My long-standing interests focus on this essential biological process and the mechanisms by which the cis-regulatory modules that govern gene expression are reprogrammed to cause dramatic changes in cell fate. Leveraging the strengths of the Drosophila system, we are defining the fundamental mechanisms that drive conserved developmental transitions. We identified specialized transcription factors that control these transitions. These factors function as pioneer factors, which are distinctive in that, unlike other transcription factors, they bind to DNA in the context of nucleosomes. This feature allows them unique access to the genome and helps to redefine the chromatin accessibility landscape. Because of their ability to reprogram cell fate, mis-expression of pioneer factors are correlated with numerous different cancers. Nonetheless, the specific functions of pioneer factors that enable efficient reprogramming and the biological barriers that restrict it remain unclear. We defined an essential role of pioneer factors in the rapid and efficient reprogramming that follows fertilization as the genomes of the specialized germ cells are unified to generate an entirely new organism. Using the power of the early Drosophila embryo, we uncovered key properties of pioneer factors in defining both the active and silent genome. We further defined roles for pioneer factors in stem-cell populations, allowing us to define general mechanisms that regulate cell-fate transitions. Building on the systems we developed, we continue to address fundamental questions regarding how multiple pioneer factors cooperate to allow for efficient genome reprogramming, what cell-type-specific features regulate pioneer activity, and how dysregulation of gene expression leads to disease. Understanding how specialized factors structure the genome to promote gene expression programs necessary for cell-fate specification will have important implications for understanding both normal development and how mis-regulation leads to disease.

About Melissa Harrison
Dr. Melissa Harrison is a Professor in the Department of Biomolecular Chemistry at the University of Wisconsin-Madison School of Medicine and Public Health, where she started her lab in 2011. As a postdoctoral fellow with Thomas Cline and Michael Botchan at the University of California, Berkeley, she initiated research into the factors that drive transcriptional activation of the zygotic genome. Her studies of transcriptional control began as an undergraduate with Kevin Struhl at Harvard University and continued as a graduate student in the laboratory of Bob Horvitz at the Massachusetts Institute of Technology. She has received a Basil O'Connor Starter Scholar Research Award, a Wisconsin Partnership Program New Investigator Award, an American Cancer Society Research Scholar Award, and a Vallee Scholar Award.

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