2025/08/01 by Courtney E. Dresden, Ekaterina P. Andrianova, Brian J. Smith +8 · 1 voice
Biochemistry, Genetics and Molecular Biology · #CRISPR and Genetic Engineering #Genomics and Chromatin Dynamics #RNA modifications and cancer
paper · pdf · doi:10.1101/2025.07.29.667167
openalex publication_date 2025/08/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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-ZIPIII) family of TFs. HD-ZIPIII activity is controlled by inputs at transcriptional, post-transcriptional, and post-translational levels. As part of their multidomain architecture, HD-ZIPIII 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-ZIPIII and HD-ZIPIV proteins contain a cryptic, deeply conserved START domain which we term the disorder-containing START domain (dSTART). The dSTART domain is required for HD-ZIPIII developmental function, controlling their subcellular localization and DNA-binding properties. The dSTART domain also helps discriminate responsive from non-responsive binding sites across the HD-ZIPIII shared genetic network. Finally, we identify candidate ligands of the dSTART domain including several species of phosphatidylglycerol and phosphatidic acid. 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.