title: A trihelix DNA binding protein counterbalances hypoxia-responsive transcriptional activation in Arabidopsis.
abstract: Transcriptional activation in response to hypoxia in plants is orchestrated by ethylene-responsive factor group VII (ERF-VII) transcription factors, which are stable during hypoxia but destabilized during normoxia through their targeting to the N-end rule pathway of selective proteolysis. Whereas the conditionally expressed ERF-VII genes enable effective flooding survival strategies in rice, the constitutive accumulation of N-end-rule-insensitive versions of the Arabidopsis thaliana ERF-VII factor RAP2.12 is maladaptive. This suggests that transcriptional activation under hypoxia that leads to anaerobic metabolism may need to be fine-tuned. However, it is presently unknown whether a counterbalance of RAP2.12 exists. Genome-wide transcriptome analyses identified an uncharacterized trihelix transcription factor gene, which we named HYPOXIA RESPONSE ATTENUATOR1 (HRA1), as highly up-regulated by hypoxia. HRA1 counteracts the induction of core low oxygen-responsive genes and transcriptional activation of hypoxia-responsive promoters by RAP2.12. By yeast-two-hybrid assays and chromatin immunoprecipitation we demonstrated that HRA1 interacts with the RAP2.12 protein but with only a few genomic DNA regions from hypoxia-regulated genes, indicating that HRA1 modulates RAP2.12 through protein-protein interaction. Comparison of the low oxygen response of tissues characterized by different levels of metabolic hypoxia (i.e., the shoot apical zone versus mature rosette leaves) revealed that the antagonistic interplay between RAP2.12 and HRA1 enables a flexible response to fluctuating hypoxia and is of importance to stress survival. In Arabidopsis, an effective low oxygen-sensing response requires RAP2.12 stabilization followed by HRA1 induction to modulate the extent of the anaerobic response by negative feedback regulation of RAP2.12. This mechanism is crucial for plant survival under suboptimal oxygenation conditions. The discovery of the feedback loop regulating the oxygen-sensing mechanism in plants opens new perspectives for breeding flood-resistant crops.
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Giuntoli
authors.affiliation: Center for Plant Cell Biology, University of California, Riverside, California, United States of America.
authors.forename: Seung Cho
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Licausi
authors.affiliation: Max Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Kosmacz
authors.affiliation: Center for Plant Cell Biology, University of California, Riverside, California, United States of America.
authors.forename: Teruko
authors.initials: T
authors.lastname: Oosumi
authors.affiliation: Institute of Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Joost T
authors.initials: JT
authors.lastname: van Dongen
authors.affiliation: Center for Plant Cell Biology, University of California, Riverside, California, United States of America.
authors.forename: Julia
authors.initials: J
authors.lastname: Bailey-Serres
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Pierdomenico
authors.initials: P
authors.lastname: Perata
mesh_terms: D017360:Arabidopsis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D018744:DNA, Plant / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D025461:Feedback, Physiological; D018506:Gene Expression Regulation, Plant; D018745:Genome, Plant; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D018515:Plant Leaves / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018520:Plant Shoots / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: D029681:Arabidopsis Proteins; D018744:DNA, Plant; D004268:DNA-Binding Proteins; C000597917:HRA1 protein, Arabidopsis; C569242:RAP2.12 protein, Arabidopsis; D014157:Transcription Factors; D010100:Oxygen