Investigating the Phase Separation Behavior of the Transcriptional Repressor Yan in Drosophila Melanogaster

Daisy Maslan Rebay Lab, University of Chicago

Abstract

Transcription factors are essential to genetic regulation. However, we do not have a good understanding of how transcriptional factors localize at sufficient concentrations to organize complexes at enhancer regions to affect genetic output. My work studies phase separation as a model that may answer this question. Broadly, phase separation can be understood as the organization of cellular components into a membraneless organelle-like condensate that exists at a different phase than the rest of its environment. Previous work has found that some transcription factors form aggregates, now understood as phase-separated bodies, which I will refer to as condensates. My work studies this model as it relates to the transcriptional repressor Yan in Drosophila Melanogaster; Yan is an evolutionarily conserved member of the E26 (ETS) transcription factor family, with its human paralogue referred to as Tel. Previous work from the Rebay lab has identified that Yan can form liquid-liquid phase separated condensates when overexpressed in the salivary glands of late third instar larva. My project aims to identify the mechanisms by which these phaseseparated condensates form, and, in the long term, to examine how the condensates influence Yan’s repressive function. My summer project had three goals: to assess the requirement for Yan DNA binding in condensate formation by generating a Yan mutant that can’t bind DNA; to ask whether the corepressor Groucho colocalizes to Yan condensates; and to identify tissues in which endogenous (rather than overexpressed) Yan forms condensates.

Hanson, MA. “Drosophilia female clip art. Specifically drosophilia melanogaster.” 11 Feb 2021.