The extra-terminal domain drives the role of BET proteins in transcription -- SLAM-seq following 25 min depletion of Bdf1/Bdf2 and overexpression of the Bdf1 ET domain

As chromatin readers, BET proteins use their tandem bromodomains to interact with acetylated lysine residues on histones and other protein partners. However, recent findings illustrate that bromodomain activity does not fully explain the role of BET proteins in transcription, highlighting the significance of other BET protein domains.

We evaluated the importance of all conserved domains of BET proteins and determined that the extra-terminal (ET) domain is essential for cell viability, genome-wide transcription and BET protein chromatin occupancy. Furthermore, we provide evidence that the ET domain performs these functions by serving as a hub for interactions with other factors involved in transcription regulation. Our findings expand current understanding of the complex biology of BET proteins and suggest a potential mechanism by which cells can bypass bromodomain inhibition in pathologic states.