Biology Seminar - Erica Larschan

"X marks the spot: Identification of the X-chromosome for coordinated gene regulation"

The mechanisms by which differential occupancy of transcription factors (TFs) at similar binding sites leads to context-specific transcriptional responses remains poorly understood. X chromosome upregulation (XCU), the most highly conserved step in dosage compensation best studied in Drosophila, serves as a model for how differential occupancy of similar TFs function context-specifically: sequence variation within GA-repeat motifs accumulated on the X-chromosome over evolutionary time to promote the binding of a specific GA-binding TF (CLAMP) that recruits the dosage compensation complex (DCC) and outcompetes another similar TF (GAF). However, the mechanism by which the CLAMP-GAF competition drives specific targeting of the DCC to the X-chromosome remains unknown. The dynamic relationship between CLAMP and GAF drives functionally divergent chromatin looping on the X-chromosome in contrast to similar looping on autosomes. We also performed the SPRITE technique developed in the Guttman lab in male versus female cells and identified sex-specific splicing hubs. Overall, we provide new insight into the mechanisms by which transcription and splicing are targeted to their precise locations in the genome over time and space.

Host: Angela Stathopoulos