MECHANISMS OF BZIP ON TRANSCRIPTIONAL REGULATION OF TARGET GENES
Through dimerization, phosphorylation, or interaction with other nuclear proteins, the specificity and affinity of bZIP binding to DNA will change, which will affect the activation of other genes, as well as its own stability and subcellular localization (Schütze et al., 2008). By forming homo- or heterodimers, binding specific gene promoters in its basic region and interacting with cis -acting elements of the promoter region, the bZIP transcription factor inhibits or activates the expression of multiple downstream related target genes, thereby participating in transcriptional regulation process.
The binding specificity of bZIP factors in plants is mainly determined by 3 bases flanking the 4 core nucleotides. Generally, bZIP factors preferentially select ACGT core palindromes or pseudo-palindromic cis -acting elements to bind, such as G-box (CACGTG), C-box (GACGTC), A-box (TACGTA), ABRE (ACGTGGC) (Izawa et al., 1993; Kim et al. 2004). Most of them are located in the ABA hormone-induced promoter region. When the bZIP protein interacts with these cis -acting elements, the N-terminus of its basic domain is inserted into the large groove of the DNA double-strand, and the C-terminus of the leucine zipper is dimerized to form a superimposed curl helix (Landschulz et al., 1988; Ellenberger et al., 1992).
G-box is one of the most common targets of bZIP transcription factors. de Vetten and Ferl (1995) firstly found that corn GBF1 is a basic region leucine zipper protein and could activate Adhl expression by binding to its G-box. After that, series of stress related genes were found to be bound at their G-box and regulated by various bZIPs. Kaminaka et al. (2006) found thatArabidopsis thaliana AtbZIP10 can combine G-box to negatively regulate plant resistance to pathogenic bacteria and other stresses. Zou et al. (2008) demonstrated that the rice OsbZIP10/OsABI5 could bind the G-box element to trans -activate the expression of stress resistance genes, thereby inhibiting seed germination and seedling growth. Liu et al. (2012) also studied rice and found that under low temperature stress,OsbZIP52 /RISBZ5 can recognize the G-box on the downstream target gene to enhance the low temperature sensitivity of rice. The Arabidopsis thalianaAtbZIP56/HY5 binds directly to the promoters of light responsible element containing the G-box and thus regulates their transcriptional activity (Yoon et al., 2006). Induced by salt, the Tamarix hispida bZIP1 bound to G-box of the stress response gene and regulated the expression of downstream genes (Ji et al., 2013). Using chromatin immunoprecipitation, Lee et al. (2006a) demonstrated that CabZIP1 binds to the G-box elements in native promoter of the hot pepper pathogenesis-related protein 1 (CaPR-1 ) gene in vivo. Shaikhali et al. (2012) identified the AtbZIP16 as a component binding to the G-box-containing promoter fragment of light-harvesting chlorophyll a/b-binding protein2.4 (LHCB2.4) from nuclear extracts of high light-treated Arabidopsis plants.
The ABRE element is also the most favorite target of bZIP transcription factors. Sun et al. (2011) found that AtbZIP1 binds to ABRE active elements and regulates the plant’s response to low temperature stress through ABA-dependent signaling pathways. Yoshida et al. (2015) demonstrated that the Arabidopsis thaliana bZIP transcription factors ABF1, ABF2, ABF3, and ABF4 combined with ABRE and regulated the expression of downstream genes related to salt and drought tolerance. In maize, ZmbZIP17 functions as an ER stress transducer, interacting with ABREs (Yang et al. 2013). Rice OsbZIP46/OsABF2 (Chang et al., 2017; Hossain et al., 2010; Tang et al. 2012a), OsbZIP52/RISBZ5 (Liu et al., 2012),OsbZIP10/OsABI5 (Zou et al., 2007; Zou et al., 2008), OsbZIP05/OSBZ8 (Mukherjee et al., 2006; Nakagawa et al., 1996) all regulate the expression of plant ABA-responsive genes by binding to the ABRE element of the target gene. Zhang et al. (2017b) proved that wheat TabZIP14-B showed transcriptional activation ability through the transactivation assay and was capable of binding the abscisic acid (ABA) responsive element (ABRE) in yeast. Wang et al. (2019) isolated and functionally characterized the sweet potato IbABF4 gene, which encodes a bZIP transcription factor. The IbABF4 protein localized to the nucleus, exhibited transcriptional activation activity, and showed binding to the cis-acting ABA-responsive element (ABRE) in vitro.
In addition, bZIP transcription factors could target on genes by C-Box and A-box. Except for G-box, the C-box of pathogenic responsive genes could also bound and negatively regulated by AtbZIP10 inArabidopsis thaliana (Kaminaka et al., 2006). Induced by ABA and drought, the Tamarix hispida bZIP1 bound to C-box and A-boxcis -elements of the stress response gene (Ji et al., 2013).
In summary, bZIP transcription factors regulate the transcriptional expression by interacting with specific cis -regulatory sequences in the promoter region of response genes to regulate plant stress tolerance (Sornaraj et al., 2016). To understand the actual relationship between bZIP subfamilies and their binding cis -regulator motifs (Table I and Figure I), all the functional annotated bZIPs were categorized into 13 known subgroups based on the method described by Corrêa et al. (2008). It seems that the G-Box and ABRE attracts most scientists’ interests and are two most understood cis -elements of bZIP transcription factors (Table I). The bZIPs bind to G-Box are categorized into subfamilies A, C, G, H, K and S; while those recognize ABRE belong to the subgroups A, B, C, G and S (Table I). Besides, there are also several reports on mechanisms about how bZIP transcription factors regulate other two cis -elements, C-box and A-box (Table I). Interestingly, the bZIPs bind to C-box are usually belong to subfamilies C and S; the functional annotated bZIP bind to A-box is classified into subfamily S. Though the number of functional annotated bZIP is limit, their binding activities of different subfamilies to specificcis -elements could also provide directional suggestions for further research on de novo bZIPs and potential targets. However, more evidences are still needed to fulfil the relevance between bZIP subfamilies and corresponding cis -elements.