UBC Math-Bio Seminar: Albert Tsai

Precise spatiotemporal patterns of transcription factors (TFs) regulate genes critical for embryo development, instructing cells to differentiate and adopt specific fates. For example, the Homeobox (Hox) TF Ultrabithorax (Ubx) specifies the identity of body segments along the anterior-posterior axis. One of its target genes is shavenbaby (svb) that fates ectodermal cells into trichomes. However, svb enhancers respond to Ubx using low-affinity binding sites and live imaging in embryos suggest that  Ubx-DNA interactions last only for a few seconds on average. Given these stochastic and transient molecular interactions, how can TFs reliably drive gene expression needed for cell-fate determination?

Using super-resolution microscopy, we showed that svb transcription sites sit in Ubx-rich sub-nuclear regions co-enriched for specific transcriptional cofactors. Genes regulated by Ubx can colocalize to the same environment, improving the robustness of transcription and phenotype development under stress. Over the course of embryogenesis, TF distributions become more heterogeneous and clustered, which may progressively favor the formation of TF environments. Understanding how the organization of TFs coordinate stochastic and transient interactions into precise and persistent regulatory signals will help decipher how multicellular eukaryotes organize their nucleus to shape their development.