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1. Epigenetic Regulation of ABA-Induced Transcriptional Responses in Maize

   https://doi.org/10.1534/g3.119.400993  

   Vendramin, Stefania; Huang, Ji; Crisp, Peter A.; Madzima, Thelma F.; McGinnis, Karen M. (May 2020, G3: Genes|Genomes|Genetics)

   Plants are subjected to extreme environmental conditions and must adapt rapidly. The phytohormone abscisic acid (ABA) accumulates during abiotic stress, signaling transcriptional changes that trigger physiological responses. Epigenetic modifications often facilitate transcription, particularly at genes exhibiting temporal, tissue-specific and environmentally-induced expression. In maize ( Zea mays ), MEDIATOR OF PARAMUTATION 1 (MOP1) is required for progression of an RNA-dependent epigenetic pathway that regulates transcriptional silencing of loci genomewide. MOP1 function has been previously correlated with genomic regions adjoining particular types of transposable elements and genic regions, suggesting that this regulatory pathway functions to maintain distinct transcriptional activities within genomic spaces, and that loss of MOP1 may modify the responsiveness of some loci to other regulatory pathways. As critical regulators of gene expression, MOP1 and ABA pathways each regulate specific genes. To determine whether loss of MOP1 impacts ABA-responsive gene expression in maize, mop1-1 and Mop1 homozygous seedlings were subjected to exogenous ABA and RNA-sequencing. A total of 3,242 differentially expressed genes (DEGs) were identified in four pairwise comparisons. Overall, ABA-induced changes in gene expression were enhanced in mop1-1 homozygous plants. The highest number of DEGs were identified in ABA-induced mop1-1 mutants, including many transcription factors; this suggests combinatorial regulatory scenarios including direct and indirect transcriptional responses to genetic disruption ( mop1-1 ) and/or stimulus-induction of a hierarchical, cascading network of responsive genes. Additionally, a modest increase in CHH methylation at putative MOP1-RdDM loci in response to ABA was observed in some genotypes, suggesting that epigenetic variation might influence environmentally-induced transcriptional responses in maize. 

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2. The Hippo effector YAP1/TEAD1 regulates EPHA3 expression to control cell contact and motility

   https://doi.org/10.1038/s41598-022-07790-4  

   Al-Mathkour, Marwah M.; Dwead, Abdulrahman M.; Alp, Esma; Boston, Ava M.; Cinar, Bekir (December 2022, Scientific Reports)

   Abstract The EPHA3 protein tyrosine kinase, a member of the ephrin receptor family, regulates cell fate, cell motility, and cell–cell interaction. These cellular events are critical for tissue development, immunological responses, and the processes of tumorigenesis. Earlier studies revealed that signaling via the STK4 -encoded MST1 serine-threonine protein kinase, a core component of the Hippo pathway, attenuated EPHA3 expression. Here, we investigated the mechanism by which MST1 regulates EPHA3. Our findings have revealed that the transcriptional regulators YAP1 and TEAD1 are crucial activators of EPHA3 transcription. Silencing YAP1 and TEAD1 suppressed the EPHA3 protein and mRNA levels. In addition, we identified putative TEAD enhancers in the distal EPHA3 promoter, where YAP1 and TEAD1 bind and promote EPHA3 expression. Furthermore, EPHA3 knockout by CRISPR/Cas9 technology reduced cell–cell interaction and cell motility. These findings demonstrate that EPHA3 is transcriptionally regulated by YAP1/TEAD1 of the Hippo pathway, suggesting that it is sensitive to cell contact-dependent interactions. 

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3. Nuclear phosphoinositide signaling promotes YAP/TAZ-TEAD transcriptional activity in breast cancer

   https://doi.org/10.1038/s44318-024-00085-6  

   Jung, Oisun; Baek, Min-jeong; Wooldrik, Colin; Johnson, Keith R.; Fisher, Kurt W.; Lou, Jinchao; Ricks, Tanei J.; Wen, Tianmu; Best, Michael D.; Cryns, Vincent L.; et al (April 2024, The EMBO Journal)

   Abstract The Hippo pathway effectors Yes-associated protein 1 (YAP) and its homolog TAZ are transcriptional coactivators that control gene expression by binding to TEA domain (TEAD) family transcription factors. The YAP/TAZ–TEAD complex is a key regulator of cancer-specific transcriptional programs, which promote tumor progression in diverse types of cancer, including breast cancer. Despite intensive efforts, the YAP/TAZ–TEAD complex in cancer has remained largely undruggable due to an incomplete mechanistic understanding. Here, we report that nuclear phosphoinositides function as cofactors that mediate the binding of YAP/TAZ to TEADs. The enzymatic products of phosphoinositide kinases PIPKIα and IPMK, including phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) and phosphatidylinositol 3,4,5-trisphosphate (P(I3,4,5)P₃), bridge the binding of YAP/TAZ to TEAD. Inhibiting these kinases or the association of YAP/TAZ with PI(4,5)P₂and PI(3,4,5)P₃attenuates YAP/TAZ interaction with the TEADs, the expression of YAP/TAZ target genes, and breast cancer cell motility. Although we could not conclusively exclude the possibility that other enzymatic products of IPMK such as inositol phosphates play a role in the mechanism, our results point to a previously unrecognized role of nuclear phosphoinositide signaling in control of YAP/TAZ activity and implicate this pathway as a potential therapeutic target in YAP/TAZ-driven breast cancer. 

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4. Ethylene-independent modulation of root development by ACC via downregulation of WOX5 and group I CLE peptide expression

   https://doi.org/10.1073/pnas.2417735122  

   Mou, Wangshu; Khare, Ria; Polko, Joanna K; Taylor, Isaiah; Xu, Juan; Xue, Dawei; Benfey, Philip; Van_de_Poel, Bram; Chang, Caren; Kieber, Joseph J (February 2025, Proceedings of the National Academy of Sciences)

   In seed plants, the canonical role of 1-aminocyclopropane-1-carboxylic acid (ACC) is to serve as the precursor in the biosynthesis of the phytohormone ethylene, and indeed, ACC treatment is often used as a proxy for ethylene treatment. Increasing evidence suggests that ACC can also act independently of ethylene to regulate various aspects of plant growth and development. Here, we explore the effects of ACC onArabidopsis thalianaroot growth and the mechanisms by which it acts. ACC inhibits growth of the primary root inArabidopsisseedlings when ethylene signaling is blocked, which becomes evident after 36 h of treatment with ACC. This reduced root growth is in part the result of suppressed cell proliferation in the root meristem resulting from altered expression of a key regulator of stem cell niche activity, WOX5. ACC also promotes lateral root (LR) development, in contrast to ethylene, which inhibits LR formation. Transcriptomic analysis of roots revealed no significant changes in gene expression after 45 min or 4 h of ACC treatment, but longer treatment times revealed a large number of differentially expressed genes, including the downregulation of the expression of a small group of phylogenetically related CLE peptides. Reduced expression of these group 1 CLEs in response to ACC leads to the activation of a transcription factor, LBD18, which promotes LR development. These results suggest that ACC acts to modulate multiple aspects ofArabidopsisroot growth independently of ethylene via distinct transcriptional effects in the root meristem and LR precursor cells. 

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5. Evaluating Regulatory Module Function within Mitochondrial Pyruvate Dehydrogenase Complex

   https://doi.org/10.1101/2025.11.24.690278  

   Keller, Caroline; Caseys, Celine; Kliebenstein, Daniel J (November 2025, bioRxiv)

   Abstract Regulatory networks coordinate metabolism to control how plants adapt to biotic and abiotic stresses. This coordination can align transcriptional shifts across metabolic pathways using cis-regulatory elements shared across the enzyme genes within these pathways. While the role of transcription factors (TFs) in controlling this process across pathways is well known, less is known regarding the role of shared cis-regulatory elements across the genes in a pathway. Sharing cis-regulatory elements across the genes in an enzyme complex or pathway, can create coordinated regulation of the pathway by a TF. However, it is unclear if all the genes in a pathway or enzyme complex need to be fully coordinated for maximal function. For example, if one gene in an enzyme complex loses a cis-regulatory element, it may not alter the function of the enzyme complexes function if post-transcriptional or compensatory transcriptional changes are sufficient to balance the complex. To test how cis-modular membership shapes the function of an enzyme complex, we used CRISPR/Cas9 to abolish a common cis-regulatory element across the promoters of nine genes required for the mitochondrial pyruvate dehydrogenase complex (mtPDC). This complex is composed of three apoenzymes and is a central hub coordinating carbon flow between glycolysis and the tricarboxylic acid (TCA) cycle. Different combinations of these cis-element mutations were tested across the genes in the complex inArabidopsis thalianaand the created genotypes were phenotyped for altered enzyme function using digital growth analysis, disease assays, metabolomics, and transcriptomics. This analysis revealed that mutating cis-element motifs of genes in this enzyme complex produced distinct phenotypes, displaying promoter-specific buffering and modularity. 

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