FEATURING KEYNOTE SPEAKER:
Antonio Giraldez, PhD
Fergus F. Wallace Professor of Genetics
Chair, Genetics
Yale School of Medicine
Expanding our knowledge of genome activation through epigenomics and expansion microscopy
Development begins with a single-cell zygote, the product of the union of sperm and oocyte. Upon fertilization, the zygotic genome undergoes extensive developmental reprogramming during the Maternal-to-Zygotic transition (MZT), which confers a totipotent state upon the zygote. This universal step in animal development results in the activation of the zygotic genome, the reprogramming of maternally inherited regulators, and the initiation of embryonic development. My laboratory investigates the mechanisms that regulate the activation of the genome and the post-transcriptional regulation of the maternal mRNAs with the goal of drawing common principles in biology.
In this seminar I will present our recent research on the mechanisms that control genome activation and the sequence of events that dictate chromatin reprogramming to stablish developmental competency during genome activation. I will further discuss our recent work on using imaging and expansion microscopy to directly visualize the interplay between changes in chromatin structure and transcriptional activation during cellular reprogramming. We have developed a super-resolution imaging method termed Chromatin Expansion Microscopy (ChromExM) that is capable of resolving individual nucleosomes with multimodal labelling capabilities in developing embryos, approaching ~3nm resolution. Using this method we have visualized the interaction between transcription factors and nucleosomes, the recruitment of RNA Pol II to specific genes by TFs, and transcribing RNA Poll II in string-like nanostructures associated with nascent RNAs. I will discuss how these methods have provided a new model for transcriptional activation and how ChromExM is a broadly applicable method to uncover principles of transcriptional organization and enhancer-promoter interactions during genome activation.