AP2/ERF Transcription Factor Regulatory Networks in Hormone and Abiotic Stress Responses in Arabidopsis

Abstract

Dynamic environmental changes such as extreme temperature, water scarcity and high salinity affect plant growth, survival, and reproduction. Plants have evolved sophisticated regulatory mechanisms to adapt to these unfavorable conditions, many of which interface with plant hormone signaling pathways. Abiotic stresses alter the production and distribution of phytohormones that in turn mediate stress responses at least in part through hormone- and stress-responsive transcription factors. Among these, the APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) family transcription factors (AP2/ERFs) have emerged as key regulators of various stress responses, in which they also respond to hormones with improved plant survival during stress conditions. Apart from participation in specific stresses, AP2/ERFs are involved in a wide range of stress tolerance, enabling them to form an interconnected stress regulatory network. Additionally, many AP2/ERFs respond to the plant hormones abscisic acid (ABA) and ethylene (ET) to help activate ABA and ET dependent and independent stress-responsive genes. While some AP2/ERFs are implicated in growth and developmental processes mediated by gibberellins (GAs), cytokinins (CTK), and brassinosteroids (BRs). The involvement of AP2/ERFs in hormone signaling adds the complexity of stress regulatory network. In this review, we summarize recent studies on AP2/ERF transcription factors in hormonal and abiotic stress responses with an emphasis on selected family members in Arabidopsis. In addition, we leverage publically available Arabidopsis gene networks and transcriptome data to investigate AP2/ERF regulatory networks, providing context and important clues about the roles of diverse AP2/ERFs in controlling hormone and stress responses.

Keywords: AP2/ERF; gene regulatory network; plant growth; plant hormones; plant stress.

FIGURE 1

General regulatory mechanisms of AP2/ERF family transcription factors. AP2/ERFs are regulated by multiple stresses and stimuli at transcription, translation and protein modification levels. Upon stresses, AP2/ERFs are induced though cis-elements presented in their promoter regions (left bottom). These cis-elements include HSE, EBS, LRT, ABRE and many other unknown binding sites that respond to HSFAs, EIN3, ICE, AREBs and other transcription factors, respectively. The transcription of AP2/ERFs is also regulated by HDACs. Alternative splicing helps generate AP2/ERFs functional mRNA (left). Under normal condition, AP2/ERFs have adverse effect on plant growth and development and thus need to be eliminated. miroRNA mediated AP2/ERF silence is one of the ways to inhibit AP2/ERFs translation (left). E3 ubiquitin ligases involved proteasome degradation and phosphorylation mediated by kinases provide additional ways to regulate AP2/ERFs protein levels and activity (middle). These E3 ligases include DRIP1/2, RGLG1/2, SINA2, and PRT6, which mediate DREB2A, ERF53, RAP2.2, and ERF-VIIs degradation, respectively. ERF-VIIs undergo N-end rule mediated degradation under normal condition. BPM provides RAP2.4 docking adaptor for CUL3-E3 complex. MPKs and SnRKs mediated phosphorylation activates and represses ERF104 and RAV1 function, respectively. Under stresses, AP2/ERFs including CRFs and ERF-VIIs translocate into nucleus, bind to conserved or diverged DNA binding sites, interact with many other transcription factors and histone modification complex to either activate or repress stress responsive genes expression (right). Among stress induced genes, RbohD is responsive for ROS and H₂O₂ generation. Induced H₂O₂ serves as a signal messenger to active ROS scavenging enzyme genes and stress responsive genes expression. Figure is created with BioRender.

FIGURE 2

Overview about AP2/ERFs mediated abiotic stresses. Members in DREBs and ERFs subfamily positively regulate numerous abiotic stresses, but negatively regulate plant growth. The ability to regulate several stresses simultaneously form a comprehensive regulatory network. Among the network, DREB-A1 family might act as repressors at the upstream of DREBs with question mark. Arrows and bar ends indicate activation and repression effect, respectively. Figure is created with BioRender.

FIGURE 3

AP2/ERFs roles in hormone pathways. Abiotic stresses alter the production and distribution of phytohormones that in turn mediate stresses responses through hormone signaling components and AP2/ERFs. Arrows and bar ends indicate activation and repression effect, respectively. Figure is created with BioRender.

FIGURE 4

AP2/ERFs regulatory network in abiotic stresses and hormones. (A) Arabidopsis AP2/ERFs in abiotic stresses and hormone responsive gene co-expression networks. Networks from Chockalingam et al. (2016) and Chockalingam et al. (2017) were used to investigate the functions of AP2/ERFs. The color legend indicates normalized p-value for the enrichment of the indicated hormone- or stress-responsive gene set by Fisher’s exact test. (B) Venn diagram showing overlaps among CBFs-regulated genes compared with cold-regulated, ET-regulated and BR-regulated genes (left). Venny (http://bioinfogp.cnb.csic.es/tools/venny/index.html) was used to perform the comparisons. The significance of overlapping genes regulated by CBFs versus cold, ET and BR is calculated by hypergeometric test (right). (C) CBFs regulated cold response pathway with integration of ET and BR signaling components. Panel (C) is created with BioRender.