A cryptic START domain regulates deeply conserved transcription factors.

Transcription factors (TFs) integrate a diverse array of inputs to achieve the exquisite control of gene expression necessary for life. In plants, this is exemplified by the deeply conserved CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-Zip III) family of TFs. HD-Zip III activity is controlled by inputs at transcriptional, post-transcriptional, and post-translational levels. As part of their multidomain architecture, HD-Zip III TFs contain a StAR-related lipid transfer (START) domain, a ubiquitously distributed evolutionary module that binds various types of lipophilic ligands. Here, we show that HD-Zip III and HD-Zip IV proteins contain an additional cryptic, deeply conserved START domain which we term the disorder-containing START domain (dSTART). The dSTART domain is required for HD-Zip III developmental function, promoting homodimerization and controlling subcellular localization and DNA-binding competence. The dSTART domain also helps discriminate responsive from nonresponsive binding sites across the HD-Zip III shared genetic network. Finally, we identify candidate ligands of the dSTART domain including several species of phosphatidylglycerol. The identification and functional characterization of a cryptic START domain provides new mechanistic insights into a deeply conserved family of TFs with roles in nearly all aspects of plant development.