The Department of Chemical and Systems Biology Presents

Mike Levine, PhD
Director, Lewis-Sigler Institute for Integrative Genomics
Princeton University

“Transcription hubs and the evolution of novel cell types”

My lab uses a combination of quantitative live imaging, genome editing and Micro-C XL assays to visualize long-range enhancer-promoter communication in living Drosophila embryos.  These studies suggest that enhancers nucleate the formation of transcriptional hubs containing clusters or condensates of RNA Polymerase II.  These hubs permit co-regulation of linked genes that are sometimes separated by hundreds of kilobase pairs.  I will present evidence for “tethering elements” as key mediators of hub formation.

We are also interested in the evolution of novel cell types in vertebrates, including neural crest, cranial placodes and specialized neuronal subtypes in the brain.  Towards this goal we have conducted systematic single cell RNA sequencing assays in a simple proto-vertebrate, the sea squirt Ciona intestinalis. The resulting high-resolution transcriptome trajectories permitted the elucidation of a comprehensive brain map, including a neuronal circuit that triggers the onset of metamorphosis in response to short wavelength light (twilight). Comparative single cell studies suggest that this circuit is related to the saccus vasculosus of nontropical fishes, a specialized structure in the hypothalamus that is responsible for photoperiodism and seasonal reproduction.

Reading Material:

1. Visualization of Transvection in Living Drosophila Embryos. Lim et al., 2018, Molecular Cell 70, 287–296. April 19, 2018 ª 2018 Elsevier Inc. https://doi.org/10.1016/j.molcel.2018.02.029
2. Comprehensive single-cell transcriptome lineages of a proto-vertebrate. Cao, C., Lemaire, L.A., Wang, W. et al. Nature 571, 349–354 (2019). https://doi.org/10.1038/s41586-019-1385-y

For Zoom link, please contact ycervant@stanford.edu