Biomolecular condensates of Eya drive transcriptional co-activation associated with eye development

Abstract

Eyes absent (Eya), a transcriptional coactivator essential for eye development in Drosophila, also plays an important role in organ development in mammals and is associated with several diseases. To better understand the mechanism of Eya-mediated transcriptional co-activation, we find that Eya forms biomolecular condensates with liquid-like properties. These condensates function as possible transcription hubs, through the compartmentalization of key eye development regulators, the transcription factors So, Dac, Optix, Ey, and the kinase Nemo, RNA Pol II machinery, P300/CBP, and show the presence of target RNAs. We map the PST-TPM-PST region of Eya, which is critical for transcriptional co-activation and eye development, to be crucial for condensate formation as well. We identify a human deafness-associated mutation mapping to a conserved Drosophila site in the PST-TPM-PST region, which impairs transcriptional co-activation and shifts the material property of the Eya condensates to a less dynamic state. Our findings thus provide evidence that the condensation of Eya and its dynamic state are integral to transcription regulation and its role in development and disease mechanisms.