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Results for “Leucine Zippers”

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At least 19 recordsLinked to original sources

PubMed2026

Genome-wide characterization of the bZIP gene family in Rattus norvegicus and expression profiling analysis during brain development.

BACKGROUND: The brown rat (Rattus norvegicus) serves as a cornerstone model organism in biomedical research, particularly for understanding physiological homeostasis and stress responses. The basic leucine zipper (bZIP) transcription factor family is a pivotal regulatory network involved in growth, organogenesis, and neurodevelopment. Despite its importance, a systematic characterization of the bZIP gene family in rats has remained elusive. RESULTS: In this study, we performed a genome-wide identification of 61 RnbZIP genes, which were categorized into 10 distinct subfamilies based on phylogenetic relationships and chromosomal localization. Structural analysis revealed conserved motif arrangements within subfamilies, while collinearity analysis identified significant gene duplication events-predominantly tandem and segmental duplications-that have driven the evolutionary expansion of the RnbZIP family. Quantitative analysis showed that members within the same subfamily shared 45%-92% sequence similarity (calculated using the BLOSUM62 scoring matrix), and all duplicated gene pairs underwent strong purifying selection (Ka/Ks < 1). Comparative genomics across seven rodent species further underscored the evolutionary conservation and divergence of these factors. Expression profiling across diverse organs and brain developmental stages indicated that RnbZIP genes exhibit high tissue specificity. Notably, 10 candidate genes, including RnbZIP01, RnbZIP02, and RnbZIP08, demonstrated dynamic expression patterns during brain maturation, suggesting their essential roles in neurodevelopmental processes. CONCLUSIONS: Our findings provide a comprehensive structural and evolutionary framework for the RnbZIP gene family, highlighting their potential regulatory functions in rat organogenesis and brain development. This study establishes a valuable resource for further functional characterization of specific bZIP members in mammalian neurological systems.

Animals↗

PubMed2026

The bZIP54 (GBF2)-SARD1 module regulates salicylic acid-mediated resistance to Pst DC3000 in Arabidopsis.

Salicylic acid (SA)-mediated defense responses are crucial for plant immunity, yet transcription factors (TFs) that coordinate SA biosynthesis with immune activation remain incompletely characterized. Here, a basic leucine zipper (bZIP) TF, bZIP54, was identified as a positive regulator in response to Pseudomonas syringae pv. tomato (Pst) DC3000. Consistent with this finding, bZIP54 regulated SA accumulation and a suite of SA-related defense genes following Pst DC3000 infection. Mechanistically, bZIP54 directly bound to a G-box-like motif in the SARD1 promoter, activating its expression-an interaction that was further enhanced by SA. Genetic analysis demonstrated that SARD1 operates downstream of bZIP54 to confer resistance to Pst DC3000. Additionally, bZIP54 also contributed to defense against the fungal pathogen Sclerotinia sclerotiorum, indicating a broader role in plant immunity. Together, these findings revealed a bZIP54-SARD1 regulatory module, thus providing insights into the transcriptional networks governing disease resistance in Arabidopsis.

Arabidopsis↗

PubMed2026

TGA6 directly activates ABF2 and ABF3 to promote leaf senescence in Arabidopsis thaliana.

Leaf senescence is a tightly regulated developmental process governed by a complex transcriptional network. Although the TGACG motif-binding (TGA) family of basic leucine zipper (bZIP) transcription factors are well-characterized regulators of plant defense responses, their roles in leaf senescence remain poorly understood. Here, we report that overexpression of TGA6 in Arabidopsis thaliana promotes early leaf senescence. Independent TGA6-overexpressing lines displayed premature leaf yellowing and significantly lower chlorophyll levels than wild-type (WT) plants under both normal growth and dark-induced senescence conditions. At the molecular level, RT-qPCR analysis revealed significant upregulation of canonical senescence marker genes, including NYC1, PAO, SAG12, SAG13, SGR1, and SGR2, in the TGA6-OE lines relative to WT plants. Furthermore, we found that the transcript levels of ABA-responsive element binding factor 2 (ABF2) and ABF3, which act upstream of these senescence markers, were significantly elevated in the TGA6-OE lines. Dual-luciferase reporter assays and electrophoretic mobility shift assay demonstrated that TGA6 directly binds to the TGACG motifs within the promoters of ABF2 and ABF3 to activate their transcription. Collectively, these findings demonstrate that TGA6 functions as a positive regulator of leaf senescence.

Arabidopsis↗

PubMed2026

Identification and analysis of HD-ZIP transcription factors that regulate salt gland development and salt tolerance in Limonium bicolor.

Soil salinity severely constrains agricultural production. Elucidating the salt-tolerance mechanisms of halophytes can provide innovative approaches for improving the salt tolerance of crop plants. In this study, we performed genome-wide identification and analysis of 36 LbHDZ genes encoding homeodomain-leucine zipper (HD-ZIP) transcription factors in Limonium bicolor, a typical recretohalophyte that excretes excess salt ions through specialized salt glands. Expression profiling across different stages of salt gland development, as well as in various tissues under salt stress, indicated that multiple LbHDZ genes are involved in regulating salt gland development and salt tolerance. Among these genes, LbHDZ14 (a member of the HD-ZIP II subfamily) exhibited sustained high expression during the critical period of salt gland formation, while its transcript levels were significantly downregulated in leaves and roots under salt stress. Subsequent experiments demonstrated that LbHDZ14 is localized in the nucleus and negatively regulates salt gland density and salt tolerance by directly binding to the promoter of LbGDSL, a positive regulator of salt gland development. In conclusion, this study reveals the expression patterns of LbHDZ genes in L. bicolor, characterizes the functional mechanism of LbHDZ14, further elucidates the regulatory network underlying salt gland development, and provides candidate genes for enhancing crop salt tolerance.

Plumbaginaceae↗

PubMed2026

Genome-Wide Characterization of the Apple HD-Zip IV Gene Family and Functional Validation of MdHDZIV3 Under PEG-Induced Osmotic Stress.

The homeodomain-leucine zipper IV (HD-Zip IV) transcription factor subfamily plays essential roles in epidermal development, cuticle formation, lipid metabolism, and environmental adaptation in plants. Despite its biological importance, the HD-Zip IV family has not been systematically characterized in apple (Malus domestica). Here, we identified 17 apple HD-Zip IV genes and named them MdHDZIV1-MdHDZIV17 based on their locations on the chromosomes. The 17 genes showed a nonuniform distribution on eight chromosomes, while the occurrence of both tandem and segmental duplications indicated that family expansion involved more than one duplication mechanism. All MdHDZIV proteins contained the conserved HD, LZ, START, and SAD domains but lacked the MEKHLA domain, consistent with typical HD-Zip IV structural features. Phylogenetic analysis classified MdHDZIV proteins into five groups together with HD-Zip IV members from Arabidopsis thaliana and rice, indicating evolutionary conservation of this subfamily. Collinearity and Ka/Ks analyses revealed that duplicated MdHDZIV gene pairs were mainly subjected to purifying selection. Promoter scanning revealed diverse cis-regulatory motifs associated with hormonal signaling, environmental stress, light response, and epidermal regulation, including ABRE, ARE, W-box, MYC, G-box, and L1-box motifs. Integration of transcriptomic profiling with qRT-PCR validation revealed pronounced tissue-dependent differences in the expression of MdHDZIV genes in leaf, fruit skin, and branch bark. Under PEG6000-induced osmotic stress and NaCl-induced salt stress, 10 candidate MdHDZIV genes displayed gene-specific and stress type-specific expression patterns, with MdHDZIV3 showing strong induction under PEG6000 treatment. Functional validation in apple calli showed that MdHDZIV3 overexpression enhanced PEG tolerance, increased fresh weight, elevated SOD and POD activities, and reduced MDA accumulation under osmotic stress. These findings provide a genome-wide framework for understanding the apple HD-Zip IV gene family.

abiotic stress↗

PubMed2026

Genome-wide identification of the peanut HD-Zip gene family and AhHDZ15 positively regulating salt and drought stress in heterologously overexpressed Arabidopsis.

Homeodomain-leucine zipper (HD-Zip) transcription factors play important roles in plant growth, development, and abiotic stress responses. However, bioinformatic analyses and functional studies of HD-Zip family in peanut are scarce. In this study, 128 AhHDZ genes were identified and classified into four subfamilies in the phylogenetic analysis. Transcriptomic data and RT-qPCR analysis indicated the expression levels of AhHDZ4 and AhHDZ15 were significantly elevated in response to 12 h of salt stress, while AhHDZ4/15/60/69/126 all showed a progressive increase over time in response to drought stress. AhHDZ15 protein was localized in the nucleus. Under salt and drought stress, the germination rates of AhHDZ15-overexpressing in Arabidopsis were significantly higher than wild-type (WT), and root lengths were also significantly longer than WT. In addition, the SOD, CAT, chlorophyll content, and Relative Leaf Water Content (RLWC) value of leaves in AhHDZ15-overexpressing lines were significantly higher than WT, while the MDA content was significantly lower than WT. The above results indicate that heterologous overexpression of AhHDZ15 enhanced salt and drought tolerance in Arabidopsis. Furthermore, AhHDZ15 could bind to the L1-box element of the AhVNI2 promoter, thereby activating AhVNI2 transcription and enhancing the expression of downstream salt stress-responsive genes. These findings implies a potential function of AhHDZ15 in peanut that requires further validation.

Arabidopsis↗

PubMed2005

Relative contribution of PDX-1, MafA and E47/beta2 to the regulation of the human insulin promoter.

The insulin promoter binds a number of tissue-specific and ubiquitous transcription factors. Of these, the homoeodomain protein PDX-1 (pancreatic duodenal homeobox factor-1), the basic leucine zipper protein MafA and the basic helix-loop-helix heterodimer E47/BETA2 (beta-cell E box transactivator 2; referred to here as beta2) bind to important regulatory sites. Previous studies have shown that PDX-1 can interact synergistically with E47 and beta2 to activate the rat insulin 1 promoter. The aim of the present study was to determine the relative contribution of PDX-1, MafA and E47/beta2 in regulating the human insulin promoter, and whether these factors could interact synergistically in the context of the human promoter. Mutagenesis of the PDX-1, MafA and E47/beta2 binding sites reduced promoter activity by 60, 74 and 94% respectively, in INS-1 beta-cells. In the islet glucagonoma cell line alphaTC1.6, overexpression of PDX-1 and MafA separately increased promoter activity approx. 2.5-3-fold, and in combination approx. 6-fold, indicating that their overall effect was additive. Overexpression of E47 and beta2 had no effect. In HeLa cells, PDX-1 stimulated the basal promoter by approx. 40-fold, whereas MafA, E47 and beta2 each increased activity by less than 2-fold. There was no indication of any synergistic effects on the human insulin promoter. On the other hand, the rat insulin 1 promoter and a mutated version of the human insulin promoter, in which the relevant regulatory elements were separated by the same distances as in the rat insulin 1 promoter, did exhibit synergy. PDX-1 was shown further to activate the endogenous insulin 1 gene in alphaTC1.6 cells, whereas MafA activated the insulin 2 gene. In combination, PDX-1 and MafA activated both insulin genes. Chromatin immunoprecipitation assays confirmed that PDX-1 increased the association of acetylated histones H3 and H4 with the insulin 1 gene and MafA increased the association of acetylated histone H3 with the insulin 2 gene.

Animals↗

PubMed2026

Genus-Wide Pan-Genome Analysis of Populus bZIP Transcription Factors with Reanalysis of Public Salt-Stress Transcriptomes.

Basic leucine zipper (bZIP) transcription factors regulate plant development and stress responses, but their genus-wide diversity in Populus remains unclear. We analyzed 19 Populus genomes and retained 1764 bZIP proteins, including 21 independent new loci and four annotation corrections. Of these, 1762 were assigned to 79 orthologous gene groups (OGGs), comprising 43 core, 20 soft-core, 15 shell and one cloud OGG, of which 59 showed copy-number variation. Phylogenetic analysis assigned 74 representative pangenes to 13 subfamilies, with five remaining unclassified and motif patterns differing among subfamilies. Whole-genome duplication (WGD)/segmental duplication accounted for 81.0% of OGG-assigned proteins and contributed predominantly to the conserved component. Although 72.2% of bZIP proteins overlapped a transposable element within the gene body or 2-kb flanks, this proportion was modestly lower than in matched non-bZIP genes, and copy-number-variable OGGs showed no greater TE coverage than invariant OGGs. Among retained homologous comparisons, 97.6% had Ka/Ks ≤ 1, supporting predominant purifying selection. Across the heterogeneous public salt-stress RNA-seq datasets analyzed, no OGG showed a significant, directionally concordant response in at least two Populus taxa. These results reveal a conserved bZIP framework shaped mainly by ancient duplication alongside variable genomic contexts and transcriptional responses.

Populus↗

PubMed2014

Distinct contributions of Aire and antigen-presenting-cell subsets to the generation of self-tolerance in the thymus.

The contribution of thymic antigen-presenting-cell (APC) subsets in selecting a self-tolerant T cell population remains unclear. We show that bone marrow (BM) APCs and medullary thymic epithelial cells (mTECs) played nonoverlapping roles in shaping the T cell receptor (TCR) repertoire by deletion and regulatory T (Treg) cell selection of distinct TCRs. Aire, which induces tissue-specific antigen expression in mTECs, affected the TCR repertoire in a manner distinct from mTEC presentation. Approximately half of Aire-dependent deletion or Treg cell selection utilized a pathway dependent on antigen presentation by BM APCs. Batf3-dependent CD8α⁺ dendritic cells (DCs) were the crucial BM APCs for Treg cell selection via this pathway, showing enhanced ability to present antigens from stromal cells. These results demonstrate the division of function between thymic APCs in shaping the self-tolerant TCR repertoire and reveal an unappreciated cooperation between mTECs and CD8α⁺ DCs for presentation of Aire-induced self-antigens to developing thymocytes.

Animals↗

PubMed2026

The transcription factor BACH1 couples chromatin priming and repression to enable macrophage plasticity and adaptation.

Macrophage activation and tissue adaptation involve precise transcriptional control by lineage-determining transcription factors (LDTFs) and stimulus-dependent TFs. The heme-regulated transcriptional repressor BACH1 clusters with myeloid LDTFs in unstimulated macrophages, suggesting a role in shaping macrophage identity and function. We found that BACH1 bound to both inactive and active regulatory regions, including latent enhancers. BACH1 recruited the NuRD complex and had dual functions, establishing early chromatin accessibility while actively repressing transcription. Upon inflammatory stimulation, BACH1 rapidly redistributed in cis to nearby promoters, reshaping chromatin occupancy, motif specificity, and enhancer-promoter interactions. BACH1 constrained 3D chromatin architecture, limiting enhancer mobility and TF complex dynamics. In vivo, Bach1 deletion impaired macrophage polarization and tissue adaptation and limited resilience during systemic and regenerative inflammation. Thus, BACH1 acts as an early chromatin accessibility-priming factor while actively repressing transcription-a regulatory activity that can be defined as pioneer repression-thereby shaping the macrophage epigenome in response to inflammatory and tissue contexts.

Basic-Leucine Zipper Transcription Factors↗

PubMed2025

TRIM63 Overexpression in FISH-Negative MiTF Family Altered Renal Cell Carcinoma (MiTF RCC).

TFE3 and TFEB break-apart fluorescent in situ hybridization (FISH) assays are the "gold standard" for diagnostic confirmation of microphthalmia-associated transcription factor (MiTF) family-altered renal cell carcinoma (MiTF RCC), which includes TFE3-rearranged RCC and TFEB-altered RCC. However, FISH assays, for multiple reasons, may lead to equivocal or false-negative results, especially in cryptic fusions resulting from intrachromosomal inversions involving 5' partner genes, such as non-POU domain-containing octamer-binding protein (NONO); GRIPI-associated protein 1 (GRIPAP1); RNA-binding motif protein, X chromosome (RBMX); and RNA-binding motif protein 10 (RBM10). When FISH results are negative in cases with strong morphological suspicion of the listed tumor entities, pathologists may recommend targeted RT-PCR or panel-based RNA fusion sequencing for diagnostic confirmation. Our recent RNA in situ hybridization (RNA ISH)-based study demonstrated RNA expression of the tripartite motif containing 63 (TRIM63) to be highly enriched in TFE3-rearranged RCC and TFEB-altered RCC, including 2 FISH false-negative RCC cases harboring RBM10::TFE3 fusion. Based on these observations, we hypothesized that TRIM63 positivity could aid in diagnosing cases that are negative by conventional FISH assay but remain morphologically suspicious, representing an unmet clinical need in this area. We collected 20 RCC cases with morphological suspicion (with equivocal/indeterminate immunohistochemistry panel) of MiTF RCC, which were TRIM63 positive, negative/equivocal for TFE3/TFEB gene rearrangement by FISH, and underwent next-generation sequencing (NGS). On NGS correlation, 14 of 20 (70%) FISH-negative TRIM63-positive tumors harbored an MiTF gene rearrangement. In the remaining 6 cases, we were unable to fully ascertain the MiTF rearrangement status due to the inherent limitation of the NGS panel utilized. The cases with MiTF gene rearrangement include TFE3 rearrangement in 60% (12/20) and TFEB low-level copy gains (with an additional missense mutation in 1 case) in 10% (2/20) of samples. RBM10:TFE3 fusion was seen in 67% (8/12) of TFE3-rearranged RCC in this cohort. TRIM63 RNA ISH assay could aid in identifying cases that harbor TFE3 or TFEB rearrangement associated with false-negative or equivocal TFE3/TFEB FISH results, especially those involving gene fusions with a paracentric Xp11 inversion. Overall, employment of TRIM63 RNA ISH coupled with TFE3/TFEB FISH assays and follow-up genomic interrogation enhanced diagnostic accuracy for patients with MiTF RCC.

Carcinoma, Renal Cell↗

PubMed2026

Histone demethylase PHF2 drives olanzapine-induced dyslipidemia via epigenomic rewiring of hepatic lipogenic genes.

Olanzapine, an atypical antipsychotic agent, is widely used in treating psychotic disorders, yet its metabolic side effects remain a clinical concern. Emerging evidence suggests that dynamic alterations in histone methylation are implicated in olanzapine-induced hepatic lipid metabolic disorders. PHF2, a JmjC family histone demethylase mediating H3K9me2 demethylation, functions as a transcriptional repressor by regulating downstream targets. To elucidate PHF2's role in this process, we utilized an olanzapine-induced dyslipidemia rat model. ChIP-qPCR analysis demonstrated a significant reduction in dimethylated histone H3 lysine 9 (H3K9me2) on the promoters of lipogenic genes (Fasn, Acc1, Scd1) in the liver, accompanied by elevated nuclear expression of PHF2 in olanzapine-treated rats. Co-immunoprecipitation (Co-IP) assays revealed a physical interaction between PHF2 and ChREBP, a glucose-responsive lipogenic transcription factor. Olanzapine was found to enhance the formation of this complex. Overexpression of PHF2 led to upregulated protein levels of FASN/ACC1 and intracellular lipid accumulation, whereas knockdown of PHF2 using siRNA attenuated these effects. Notably, the upregulation of FASN/ACC1 expression induced by olanzapine was markedly diminished in PHF2-deficient AML12 cells via ChREBP-PHF2-mediated H3K9me2 demethylation. Additionally, olanzapine inhibited the nuclear translocation of FOXA2, a PHF2 transcriptional regulator, thereby augmenting PHF2 expression. These findings uncover a novel epigenetic mechanism underlying olanzapine-induced dyslipidemia, positioning the FOXA2-PHF2-ChREBP axis as a potential therapeutic target through modulation of hepatic histone methylation.

Animals↗

PubMed2025

High expression of Rex-orf-I and HBZ mRNAs and bronchiectasis in lung of HTLV-1A/C infected macaques.

HTLV-1 type-A rarely causes lung disease in humans, whereas HTLV-1 type-C is more frequently associated with respiratory failure and premature death. We investigated the genetic basis of HTLV-1C morbidity by constructing a chimeric HTLV-1A/CoI-L encompassing the highly divergent type C orf-I. We demonstrate that systemic infectivity of HTLV-1A and HTLV-1A/CoI-L is equivalent in macaques, but viral expression in lungs is significantly higher in HTLV-1A/CoI-L infection. In addition, bronchoalveolar-lavage immune cell dynamics differs greatly with neutrophils and monocytes producing TNF-α in HTLV-1A/CoI-L, but producing IL-10 in HTLV-1A infection. Animals infected with HTLV-1A/CoI-L develops bronchiectasis at 10 months from infection, but at the same timepoint those infected with HTLV-1A do not. HTLV-1A/CoI-L expressed a 16 kDa fusion protein (p16C) via a doubly spliced, Rex-orf-IC, mRNA able to shield T-cells from efferocytosis, a monocyte function that mitigates inflammation via clearance of apoptotic cells. The Rex-orf-IC mRNA is expressed as more frequent in the lung of HTLV-1A/CoI-L than HTLV-1A infected animals. Since defective efferocytosis is associated with lung obstructive pathologies, the data raise the hypothesis that p16C may contribute to the lung morbidity observed in HTLV-1C infection.

Animals↗

PubMed2026

Nucleosomes and IDRs suppress promiscuous GCN4 binding on minichromosomes.

Eukaryotic sequence-specific transcription factors (TFs) must find their cognate DNA targets hidden in genomic chromatin amid an excess of nonspecific sequences and degenerate motifs. Although static TF interactions with nucleosomal targets have been elucidated, how TFs efficiently search for cognate sites within native gene-sized chromatin domains has been unclear. Here we used purified Saccharomyces cerevisiae HIS3 minichromosomes and single-molecule imaging to compare association and dissociation kinetics of transcription activator GCN4 on chromatin and naked genomic DNA. GCN4 displays widespread and stable off-target binding on bare DNA because of entrapment by degenerate sites and interactions with nonspecific DNA of increasing length, indicative of one-dimensional (1D) diffusion. Nucleosome organization on the minichromosome reduces promiscuous GCN4 residence times by obstructing TF association and restricting 1D target search within nucleosome-free regions. Furthermore, the intrinsically disordered GCN4 activation domain independently enhances targeting efficiency and specificity by accelerating association-dissociation kinetics in vitro and in living cells. Altogether, both nucleosome organization and activation domains independently suppress promiscuous GCN4 binding, which, if unchecked, may cause aberrant cryptic transcription known to occur upon chromatin disruptions.

Nucleosomes↗

PubMed2024

Tailored UPRE2 variants for dynamic gene regulation in yeast.

Genetic elements are foundational in synthetic biology serving as vital building blocks. They enable programming host cells for efficient production of valuable chemicals and recombinant proteins. The unfolded protein response (UPR) is a stress pathway in which the transcription factor Hac1 interacts with the upstream unfolded protein response element (UPRE) of the promoter to restore endoplasmic reticulum (ER) homeostasis. Here, we created a UPRE2 mutant (UPRE2m) library. Several rounds of screening identified many elements with enhanced responsiveness and a wider dynamic range. The most active element m84 displayed a response activity 3.72 times higher than the native UPRE2. These potent elements are versatile and compatible with various promoters. Overexpression of HAC1 enhanced stress signal transduction, expanding the signal output range of UPRE2m. Through molecular modeling and site-directed mutagenesis, we pinpointed the DNA-binding residue Lys60 in Hac1(Hac1-K60). We also confirmed that UPRE2m exhibited a higher binding affinity to Hac1. This shed light on the mechanism underlying the Hac1-UPRE2m interaction. Importantly, applying UPRE2m for target gene regulation effectively increased both recombinant protein production and natural product synthesis. These genetic elements provide valuable tools for dynamically regulating gene expression in yeast cell factories.

Saccharomyces cerevisiae↗

PubMed2026

BACH1 orchestrates macrophage state transitions to coordinate regenerative inflammation.

Efficient tissue regeneration requires the precise coordination of inflammatory and regenerative programs, principally mediated by monocyte-derived macrophages. However, the transcriptional wiring and epigenomic processes behind complex macrophage subtype specification and transition between the different states are not known. Here we have identified the transcriptional repressor BACH1 as a critical, cell-intrinsic regulator of monocyte-derived macrophage specification during skeletal muscle regeneration. Using a myeloid-specific BACH1 knockout mouse model, we demonstrate that BACH1 deficiency disrupts the temporal coordination of monocyte-to-macrophage differentiation, leading to aberrant macrophage subsets with concurrent opposing pro- and anti-inflammatory features. Single-cell RNA-sequencing profiling reveals that BACH1 controls a core transcriptional network, including Nfkb1, Cebpb, and interferon signaling, governing inflammatory resolution and functional macrophage specialization. Mechanistically, BACH1 loss accelerates macrophage differentiation but also affects its core cellular identity, resulting in sustained, rather than declining inflammatory programs including upregulation of Il1b and thus, defective tissue remodeling. These immune alterations compromise the paracrine landscape during regenerative inflammation and impair muscle stem cell differentiation. Our findings establish BACH1 as a molecular tuner or controller that integrates early innate immune signaling with regenerative output, positioning it as a central node linking transcriptional control, immune fate decisions, and tissue repair.

Animals↗

PubMed2026

Ultraviolet-B-induced OsKOL4 promotes ABA accumulation by inhibiting OsABA8ox1 and OsABA8ox2 expression.

Ultraviolet-B (UV-B) light is a component of sunlight that influences plant survival and adaptation. UV-B induces plants to regulate their phenotypes and metabolism to increase resistance to UV-B and associated stresses. Abscisic acid (ABA) metabolism and signaling are important for plant responses to UV-B. However, the mechanisms underlying UV-B-induced ABA accumulation and signaling in rice remain poorly understood. Here, we report that ENT-KAURENE OXIDASE LIKE 4 (OsKOL4) regulates UV-B-induced responses and ABA biosynthesis. UV-B activates OsKOL4 expression via OsbZIP48, an ELONGATED HYPOCOTYL 5 (HY5) homolog that directly binds to the OsKOL4 promoter. Rice plants overexpressing OsKOL4 exhibit UV-B-induced phenotypes under normal conditions, along with ABA overaccumulation phenotypes resulting from increased ABA levels. Moreover, UV-B promotes ABA accumulation by inhibiting the expression of the ABA 8'-HYDROXYLASE1 and ABA 8'-HYDROXYLASE 2 (OsABA8ox1/2) genes through OsKOL4. OsKOL4 interacts with the transcription factor AP2/ERF ON CHROMOSOME 3 (OsAPE3), which in turn represses the transcription of OsABA8ox1/2. Furthermore, both UV-B and OsKOL4 enhance the binding of OsAPE3 to the OsABA8ox1/2 promoters. Collectively, our findings demonstrate that the OsKOL4-OsAPE3 module regulates ABA homeostasis in response to UV-B signaling by reducing ABA catabolism.

Abscisic Acid↗

PubMed2026

Positive feedback loop between RAF12 and ABI5 reinforces ABA-mediated suppression of Arabidopsis seed germination.

ABA-INSENSITIVE 5 (ABI5) is a key transcriptional regulator mediating abscisic acid (ABA)-induced suppression of seed germination. However, the downstream regulatory network through which ABI5 exerts its function remains incompletely understood. Here, by integrating ChIP-seq and RNA-seq analyses, we identify RAF12, a member of the B2 Raf-like kinase subfamily, as a direct transcriptional target of ABI5. ABI5 binds to the RAF12 promoter and activates its expression. Loss-of-function raf12 mutants exhibit reduced sensitivity to ABA during seed germination, suggesting a negative regulatory role for RAF12 in this process. Conversely, RAF12 interacts with and phosphorylates ABI5, thereby enhancing its transcriptional activity. Further analysis showed that RAF12 regulates its own kinase activity through autophosphorylation. Mutations at its phosphorylation sites significantly weaken its ability to enhance ABI5's transcriptional activity. Together, these findings uncover a positive feedback loop wherein ABI5 transcriptionally activates RAF12, which in turn reinforces ABI5 activity through phosphorylation. This module may function in parallel with the canonical SnRK2s-ABI5-mediated ABA signaling cascade, offering new mechanistic insights into the fine-tuning of ABA responses during seed germination.

Arabidopsis↗