Biology Seminar Series - December 13, 2024

Title: Repetitive Elements Compete for Epigenetic Factors During Embryonic Development

 

Abstract: Chromatin reprogramming during the earliest stages of development harmonizes the maternal and paternally inherited genomes and enables transcriptional activation in zygotes. Initially distinct parent-of-origin-based chromatin patterns become nearly indistinguishable upon stem cell formation, but mechanisms underlying such reprogramming events remain only partially understood. Using the zebrafish model, we find that the maternally inherited genome possesses a substantial number of highly accessible and transcriptionally active transposable elements in newly fertilized embryos, prior to zygotic transcriptional activation, and silencing of these elements coincides with the establishment of pluripotency at the blastula stage. Through pharmacological inhibition and genetic oblation studies, we provide evidence that transposon silencing is a rate-limiting step during maternal zygotic transition, and H3K9-methylation is responsible for silencing maternal chromatin. Our data uncover a potential mechanism in which the oocyte delivers a payload of "open" chromatin in order to delay the onset of zygotic genome activation in fertilized embryos.

 

Background: Dr. Murphy is interested in the genetics, genomics, and chromatin biochemistry of cell state transitions that occur during embryonic development and carcinogenesis. His lab focuses on understanding the mechanisms that control gene activation and silencing during cell state transitions, particularly during processes like differentiation in early embryos. They study how stem cells divide and change to form tissues and different cell types, a process driven by coordinated gene expression changes. The lab also investigates how improper changes in gene expression can lead to diseases like cancer, by altering cell identity. Using zebrafish models, mammalian stem cells, and human cancer cell lines, they explore how epigenetic marks influence gene expression and drive cell transitions. Their research combines genetics, developmental biology, DNA sequencing technologies, and bioinformatics to map protein and epigenetic changes during these processes.