DELLA Proteins Recruit the Mediator Complex Subunit MED15 to Co-activate Transcription in Land Plants

DELLA proteins are negative regulators of the gibberellin response pathway in angiosperms, acting as central hubs that interact with hundreds of transcription factors and regulators to modulate their activities. While the mechanism of transcription factor sequestration by DELLAs to prevent DNA binding to downstream targets has been extensively documented, the mechanism that allows them to act as co-activators remains to be understood. Here, we demonstrate that DELLAs directly recruit the Mediator complex to specific loci in Arabidopsis, facilitating transcription. This recruitment involves DELLA amino-terminal domain and the conserved MED15 KIX domain. Accordingly, partial loss of MED15 function mainly disrupted processes known to rely on DELLA co-activation capacity; including cytokinin-dependent regulation of meristem function and skotomorphogenic response, gibberellin metabolism feedback, and flavonol production. We have also found that the single DELLA protein in the liverwort Marchantia polymorpha is capable of recruiting MpMED15 subunits, contributing to transcriptional co-activation. The conservation of Mediator-dependent transcriptional co-activation by DELLA between Arabidopsis and Marchantia implies that this mechanism is intrinsic to the emergence of DELLA in the last common ancestor of land plants. Significance Statement DELLA proteins are plant-specific transcriptional hubs integrating environmental signals with endogenous cues. In order to regulate downstream processes, DELLAs modulate the activity of hundreds of transcription factors and transcriptional regulators in various ways. Here, we describe the molecular mechanism underlying DELLA co-activator function. We show that DELLAs act as transcriptional activators in eukaryotic cells by interacting with the Mediator complex subunit MED15. Mediator function is necessary to regulate a subset of DELLA-regulated responses that are mediated by direct co-activation of DELLA-Transcription factors complexes. We further show that this mechanism is present in bryophyte DELLAs, and thus represents a conserved mechanism of DELLA function in land plants.