Family Of Transcription Factors Research Articles

Transcription factors involved in plant responses to cadmium-induced oxidative stress

Cadmium (Cd) is a heavy metal highly toxic to living organisms. Cd pollution of soils has become a serious problem worldwide, posing a severe threat to crop production and human health. When plants are poisoned by Cd, their growth and development are inhibited, chloroplasts are severely damaged, and respiration and photosynthesis are negatively affected. Therefore, elucidating the molecular mechanisms that underlie Cd tolerance in plants is important. Transcription factors can bind to specific plant cis-acting genes. Transcription factors are frequently reported to be involved in various signaling pathways involved in plant growth and development. Their role in the resistance to environmental stress factors, particularly Cd, should not be underestimated. The roles of several transcription factor families in the regulation of plant resistance to Cd stress have been widely demonstrated. In this review, we summarize the mechanisms of five major transcription factor families–WRKY, ERF, MYB, bHLH, and bZIP–in plant resistance to Cd stress to provide useful information for using molecular techniques to solve Cd pollution problems in the future.

CRISPR/Cas9-mediated knockout of NtMYC2a gene involved in resistance to bacterial wilt in tobacco

MYC2 is a class of bHLH family transcription factors and a major regulatory factor in the JA signaling pathway, and its molecular function in tobacco has not been reported. In this study, CRISPR/Cas9-mediated MYC2 gene NtMYC2a knockout mutants at tobacco was obtained and its agronomic traits, disease resistance, and chemical composition were identified. Comparing with the WT, the leaf width of the KO-NtMYC2a was narrowed, the nornicotine content and mecamylamine content increased significantly and the resistance to Ralstonia solanacearum significantly decreased. The transcriptome sequencing results showed that DEGs related to immunity, signal transduction and growth and development were enriched between KO-NtMYC2a and WT. NtJAR1 and NtCOI1 in KO-NtMYC2a were down-regulated to regulating the JA signaling pathway, result in a significant decrease in tobacco’s resistance to R. solanacearum. Our research provides theoretical support for the functional research of MYC2 and the study of the mechanism of tobacco bacterial wilt resistance.

Investigating the mechanisms of isochorismate synthase: An approach to improve salicylic acid synthesis and increase resistance to Fusarium head blight in wheat

Salicylic acid (SA), a vital endogenous hormone, plays a crucial role in plant growth and the response to abiotic and biotic stress. Isochorismate synthase (ICS) and phenylalanine ammonia lyase (PAL) are critical rate-limiting enzymes for SA synthesis. Fusarium head blight (FHB) seriously threatens the safety of wheat production, but increasing the content of SA can enhance FHB resistance. However, the pathway of SA synthesis and regulation in wheat remains unknown. In this study, three wheat ICS (TaICSA, TaICSB, and TaICSD) were identified, and their functions were validated in vitro for isomerizing chorismate to isochorismate. The mutation of one or two homoeoalleles of TaICSA, TaICSB, and TaICSD in the wheat variety ‘Cadenza’ reduced SA levels under ultraviolet treatment and Fusarium graminearum infection, further enhancing sensitivity to FHB. Overexpression of TaICSA can significantly enhance SA levels and resistance to FHB. To further study SA synthesis pathways in wheat and avoid interference with pathogenicity related genes, the leaves of wild-type Cadenza and different TaICS mutant lines were subjected to ultraviolet treatment for transcriptomic analysis. The results showed that 37 PALs might be involved in endogenous SA synthesis, and 82 WRKY and MYB family transcription factors may regulate the expression of ICS and PAL. These results were further confirmed by RT-PCR. In conclusion, this study expands our knowledge of SA biosynthesis and identifies TaICSA, as well as several additional candidate genes that encode transcription factors for regulating endogenous SA levels, as part of an efficient strategy for enhancing FHB resistance in wheat.

CD4+CD8αα+ is the dominant phenotype of intraepithelial lymphocytes and regulated by ThPOK and Runx3 in oral lichen planus.

Oral lichen planus (OLP) is a common T cell-mediated oral mucosal immune inflammatory disease. Intraepithelial lymphocytes (IELs) are a unique subset of T cells that play an important role in regulating immune response. This study aims to investigate the phenotype and the differentiation mechanism of IELs in OLP. The expression of CD4, CD8α, CD8β, T-helper-inducing POZ/Krueppel-like factor (ThPOK), and RUNX family transcription factor 3 (Runx3) in the epithelium and peripheral blood mononuclear cells (PBMCs) of OLP was determined by immunofluorescence and immunohistochemistry. Then, the correlations among them were analyzed. Naïve CD4+ T cells were sorted from blood of OLP patients and stimulated with retinoic acid (RA) and transforming growth factor-β1 (TGF-β1). Then the expression of CD4, CD8α, CD8β, ThPOK, and Runx3 was investigated by immunocytochemistry. CD8α expression and CD8αα+ cells were upregulated in the epithelium of OLP, whereas they were downregulated in PBMCs of OLP. CD8β was not expressed in the epithelium of OLP. CD4, CD8α, and Runx3 expression and CD4+CD8α+ cells were increased, whereas ThPOK expression was decreased in the epithelium of OLP. CD8α expression was positively correlated with Runx3 expression, whereas ThPOK expression was negatively correlated with Runx3 expression. After RA and TGF-β1 stimulation, CD8α and Runx3 expression was upregulated, and ThPOK expression was downregulated in naïve CD4+ T cells. CD4+CD8αα+ IELs may be the dominant phenotype of IELs in OLP, and the differentiation of CD4+CD8αα+ IELs in OLP is negatively regulated by ThPOK and positively regulated by Runx3.

Enigmatic role of auxin response factors in plant growth and stress tolerance.

Abiotic and biotic stresses globally constrain plant growth and impede the optimization of crop productivity. The phytohormone auxin is involved in nearly every aspect of plant development. Auxin acts as a chemical messenger that influences gene expression through a short nuclear pathway, mediated by a family of specific DNA-binding transcription factors known as Auxin Response Factors (ARFs). ARFs thus act as effectors of auxin response and translate chemical signals into the regulation of auxin responsive genes. Since the initial discovery of the first ARF in Arabidopsis, advancements in genetics, biochemistry, genomics, and structural biology have facilitated the development of models elucidating ARF action and their contributions to generating specific auxin responses. Yet, significant gaps persist in our understanding of ARF transcription factors despite these endeavors. Unraveling the functional roles of ARFs in regulating stress response, alongside elucidating their genetic and molecular mechanisms, is still in its nascent phase. Here, we review recent research outcomes on ARFs, detailing their involvement in regulating leaf, flower, and root organogenesis and development, as well as stress responses and their corresponding regulatory mechanisms: including gene expression patterns, functional characterization, transcriptional, post-transcriptional and post- translational regulation across diverse stress conditions. Furthermore, we delineate unresolved questions and forthcoming challenges in ARF research.

Backbone triple resonance assignments of the dimerization domain of NF-kappaB p52 subunit.

NF-kappaB is a family of inducible transcription factors playing an important role in immune response in vertebrates. All the five members of the family function as dimers in various combinations. Though all the family members recognize and bind to similar DNA elements to regulate the transcription of its target genes, the dimer composition can lead to differential transcriptional outcomes. Here we report the backbone resonance assignment of the 24.2kDa homodimer of p52 subunit of the NF-kB family. The p52 subunit of NF-kB is a crucial player in the non-canonical NF-kB pathway and its dysregulation has shown detrimental effects in immune response leading to various inflammatory diseases and cancers. While the β-strands predicted using the backbone chemical shifts in this study largely conform with the available crystal structure, the helical turns present in the crystal structure are not observed in our results.

Abstract B019: Stearoyl-CoA desaturase is a synthetic lethal target in SMAD4-deficient cancers

Abstract Mothers against decapentaplegic homolog 4, or SMAD4, is a member of the SMAD family of transcription factors that mediate TGF-β signal transduction. SMAD4 loss of function mutation or deletion is found in about 30% of PDAC and 15% of COAD and EAC patients, and it is associated with their poor prognosis. Over the past two decades, its tumor suppressor role has been elucidated, and the loss of SMAD4 is sufficient to promote tumorigenesis in multiple GEM models. To identify novel therapeutic vulnerabilities for SMAD4-deficient cancers, a CRISPR dropout screening approach was employed in SMAD4 isogenic PDAC models. We identified stearoyl-CoA desaturase, SCD, as a synthetic lethal target in SMAD4-deficient context. SCD is critical for de novo lipid biogenesis and catalyzes the rate-limiting step in the production of monounsaturated fatty acid. Genetic and pharmacologic studies in vitro confirmed this synthetic lethal relationship. Additionally, drug-anchored CRISPR dropout screening and RNA expression profiling demonstrated that accumulation of saturated fatty acid in response to SCD inhibition drives cytotoxicity in SMAD4-deficient cells. Mouse studies with CRISPR-based knockout of SCD and a well-characterized SCD inhibitor (A939572) demonstrated anti-tumor efficacy in SMAD4-mutant xenograft models. However, compared to genetic KO of SCD the pharmacological inhibitor was less effective at inhibiting tumor proliferation in vivo. Together, these data identify SCD as a selective vulnerability in SMAD4-mutant cancers. Citation Format: Alvin Z. Lu, Silvia Fenoglio, Hsin-Jung Wu, Yingnan P. Chen. Stearoyl-CoA desaturase is a synthetic lethal target in SMAD4-deficient cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B019.

Genome-wide investigation and analysis of NAC transcription factor family in Populus tomentosa and expression analysis under salt stress.

The NAC transcription factor family is one of the largest families of TFs in plants, and members of NAC gene family play important roles in plant growth and stress response. Recent release of the haplotype-resolved genome assembly of P. tomentosa provide a platform for NAC protein genome-wide analysis. A total of 270 NAC genes were identified and a comprehensive overview of the PtoNAC gene family is presented, including gene promoter, structure and conserved motif analyses, chromosome localization and collinearity analysis, protein phylogeny, expression pattern, and interaction analysis. The results indicate that protein length, molecular weight, and theoretical isoelectric points of the NAC TF family vary, while gene structure and motif are relatively conserved. Chromosome mapping analysis showed that the P. tomentosa NAC genes are unevenly distributed on 19 chromosomes. The interchromosomal evolutionary results indicate 12 pairs of tandem and 280 segmental duplications. Segmental duplication is possibly related to amplification of P. tomentosa NAC gene family. Expression patterns of 35 PtoNAC genes from P. tomentosa subgroup were analysed under high salinity, and seven NAC genes were induced by this treatment. Promoter and protein interaction network analyses showed that PtoNAC genes are closely associated with growth, development, and abiotic and biotic stress, especially salt stress. These results provide a meaningful reference for follow-up studies of the functional characteristics of NAC genes in the mechanism of stress response and their potential roles in development of P. tomentosa.

Expression of Forkhead Box M1 and Anticancer Effects of FOXM1 Inhibition in Epithelioid Sarcoma

Epithelioid sarcoma (ES) is a rare aggressive sarcoma that, unlike most soft-tissue sarcomas, shows a tendency toward local recurrence and lymph node metastasis. Novel antitumor agents are needed for ES patients. Forkhead box transcription factor 1 (FOXM1) is a member of the Forkhead transcription factor family and is associated with multiple oncogenic functions; FOXM1 is known to be overexpressed and correlated with pathogenesis in various malignancies. In this study, we immunohistochemically analyzed FOXM1 expression levels and their clinical, clinicopathologic, and prognostic significance in 38 ES specimens. In addition, to investigate potential correlations between FOXM1 downregulation and oncologic characteristics, we treated ES cell lines with thiostrepton, a naturally occurring antibiotic that inhibits both small interfering RNA (siRNA) and FOXM1. In the analyses using ES samples, all 38 specimens were diagnosed as positive for FOXM1 by immunohistochemistry. We separated specimens into high (n = 19) and low (n = 19) FOXM1–protein expression groups by staining index score, and into large (n = 12), small (n = 25), and unknown (n = 1) tumor-size groups using a cutoff of 5 cm maximum diameter. Although there were significantly more samples with high FOXM1 expression in the large tumor group (P = .013), there were no significant differences with respect to age (P = 1.00), sex (P = .51), primary site of origin (P = .74), histologic subtypes (P = 1.00), depth (P = .74), or survival rate (P = .288) between the high and low FOXM1–protein expression groups. In the in vitro experiments using ES cell lines, FOXM1 siRNA and thiostrepton successfully downregulated FOXM1 mRNA and protein expression. Furthermore, downregulation of FOXM1 inhibited cell proliferation, drug resistance against chemotherapeutic agents, migration, and invasion and caused cell cycle arrest in the ES cell lines. Finally, cDNA microarray analysis data showed that FOXM1 regulated cIAP2, which is one of the apoptosis inhibitors activated by the TNFα-mediated NF-κB pathway. In conclusion, the FOXM1 gene may be a promising therapeutic target for ES.

Genome-Wide Identification of the TGA Gene Family and Expression Analysis under Drought Stress in Brassica napus L.

TGA transcription factors belong to Group D of the bZIP transcription factors family and play vital roles in the stress response of plants. Brassica napus is an oil crop with rich economic value. However, a systematic analysis of TGA gene family members in B. napus has not yet been reported. In this study, we identified 39 full-length TGA genes in B. napus, renamed TGA1~TGA39. Thirty-nine BnTGA genes were distributed on 18 chromosomes, mainly located in the nucleus, and differences were observed in their 3D structures. Phylogenetic analysis showed that 39 BnTGA genes could be divided into five groups. The BnTGA genes in the same group had similar structure and motif compositions, and all the BnTGA genes had the same conserved bZIP and DOG1 domains. Phylogenetic and synteny analysis showed that the BnTGA genes had a close genetic relationship with the TGA genes of the Brassica juncea, and BnTGA11 and BnTGA29 may play an important role in evolution. In addition, qRT-PCR revealed that three genes (BnTGA14/17/23) showed significant changes in eight experimental materials after drought treatment. Meanwhile, it can be inferred from the results of drought treatment on different varieties of rapeseed that the stress tolerance of parental rapeseed can be transmitted to the offspring through hybridization. In short, these findings have promoted the understanding of the B. napus TGA gene family and will contribute to future research aimed at B. napus resistant breeding.

Impact of activated charcoal on the progression of somatic embryogenesis in grape cells: Histological and transcriptomic perspectives

Somatic embryogenesis is a crucial genetic transformation method in plants. Despite numerous studies being conducted for acquiring embryogenic competence in plant cells, somatic embryo (SE) induction from embryogenic cells (ECs) has attracted relatively limited research attention. In grapes, somatic cell induction is impeded by unidentified inhibitors, which hinders the progression of globular embryo (GE) formation and subsequently embryo development. We found that addition of activated charcoal (AC) to the grape SE induction medium augmented the speed, consistency, and synchronization of embryogenesis. Cell samples cultured in the induction medium with and without AC were thoroughly evaluated through histological anatomy analysis, subcellular structure observation, and comparative transcriptomic analysis. The histological observation revealed the specific timeline of SE formation. An intermediate developmental state, referred to as the globular embryo precursor (PGE), was observed during the induction of GE formation from EC. Members of transcription factor families such as WRKY, MYB, MADS, AP2/ERF, HB-KNOX, HB-HD-ZIP, HB-WOX, NAC, and GRF were identified in the early and middle stages of GE formation. Additionally, we explored the key roles of reactive oxygen species (ROS)-, starch-, cell wall-, and hormone-related genes. The cell wall-related genes were highly enriched in differentially expressed gene sets. Several amyloplasts in EC disappeared, potentially because of hydrolysis, and numerous mitochondria were observed. In AC-added samples, starch was consumed more, and cellulose hydrolysis-related genes were downregulated, whereas cellulose synthesis-related genes had higher expression than AC-free samples. ROS response-related genes were induced when GE induction was initiated. When applied, an optimal concentration of external H2O2 promoted SE initiation in grapes, whereas a high concentration caused delayed GE formation. This study suggests that, by absorbing and releasing substances, the added AC can create a stable buffer environment for cell survival, protect against excessive ROS- or inhibitor-induced cell damage, and support uninterrupted progress of somatic embryogenesis.

BrMYB116 transcription factor enhances Cd stress tolerance by activating FIT3 in yeast and Chinese cabbage.

Cd (cadmium) is a highly toxic heavy metal pollutant often present in soil and detrimentally impacting the production and quality of horticultural crops. Cd affects various physiological and biochemical processes in plants, including chlorophyll synthesis, photosynthesis, mineral uptake and accumulation, and hormonal imbalance, leading to cell death. The MYB family of transcription factors plays a significant role in plant response to environmental influences. However, the role of MYB116 in abiotic stress tolerance remains unclear. In this study, we reported that Chinese cabbage transcription factor BrMYB116 enhanced Cd stress tolerance in yeast. The expression level of BrMYB116 was increased by Cd stress in Chinese cabbage. Additionally, yeast cells overexpressing BrMYB116 showed improved Cd stress tolerance and reduced Cd accumulation. Moreover, we found that BrMYB116 interacted with facilitator of iron transport (FIT3) to enhance Cd stress tolerance. ChIP-qPCR results showed that ScFIT3 was activated through specific binding to its promoter. Additionally, the overexpression of ScFIT3 induced Cd stress tolerance and reduced Cd accumulation in yeast and Chinese cabbage. These results suggest new avenues for plant genomic modification to mitigate Cd toxicity and enhance the safety of vegetable production.

ETV5 promotes lupus pathogenesis and follicular helper T cell differentiation by inducing osteopontin expression

Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.

Multiple transcription factors involved in the response of Chinese cabbage against Plasmodiophora brassicae.

Clubroot disease, which is caused by the obligate biotrophic protist Plasmodiophora brassicae, leads to the formation of galls, commonly known as pathogen-induced tumors, on the roots of infected plants. The identification of crucial regulators of host tumor formation is essential to unravel the mechanisms underlying the proliferation and differentiation of P. brassicae within plant cells. To gain insight into this process, transcriptomic analysis was conducted to identify key genes associated with both primary and secondary infection of P. brassicae in Chinese cabbage. Our results demonstrate that the k-means clustering of subclass 1, which exhibited specific trends, was closely linked to the infection process of P. brassicae. Of the 1610 differentially expressed genes (DEGs) annotated in subclass 1, 782 were identified as transcription factors belonging to 49 transcription factor families, including bHLH, B3, NAC, MYB_related, WRKY, bZIP, C2H2, and ERF. In the primary infection, several genes, including the predicted Brassica rapa probable pectate lyase, RPM1-interacting protein 4-like, L-type lectin-domain-containing receptor kinase, G-type lectin S-receptor-like serine, B. rapa photosystem II 22 kDa protein, and MLP-like protein, showed significant upregulation. In the secondary infection stage, 45 of 50 overlapping DEGs were upregulated. These upregulated DEGs included the predicted B. rapa endoglucanase, long-chain acyl-CoA synthetase, WRKY transcription factor, NAC domain-containing protein, cell division control protein, auxin-induced protein, and protein variation in compound-triggered root growth response-like and xyloglucan glycosyltransferases. In both the primary and secondary infection stages, the DEGs were predicted to be Brassica rapa putative disease resistance proteins, L-type lectin domain-containing receptor kinases, ferredoxin-NADP reductases, 1-aminocyclopropane-1-carboxylate synthases, histone deacetylases, UDP-glycosyltransferases, putative glycerol-3-phosphate transporters, and chlorophyll a-binding proteins, which are closely associated with plant defense responses, biosynthetic processes, carbohydrate transport, and photosynthesis. This study revealed the pivotal role of transcription factors in the initiation of infection and establishment of intracellular parasitic relationships during the primary infection stage, as well as the proliferation and differentiation of the pathogen within the host cell during the secondary infection stage.

Gene polymorphism of the family of transcription factors and their influence on the milk productivity of the first heifers

Gene polymorphism of the family of transcription factors and their influence on the milk productivity of the first heifers

Genome-Wide Identification, Characterisation, and Evolution of the Transcription Factor WRKY in Grapevine (Vitis vinifera): New View and Update.

WRKYs are a multigenic family of transcription factors that are plant-specific and involved in the regulation of plant development and various stress response processes. However, the evolution of WRKY genes is not fully understood. This family has also been incompletely studied in grapevine, and WRKY genes have been named with different numbers in different studies, leading to great confusion. In this work, 62 Vitis vinifera WRKY genes were identified based on six genomes of different cultivars. All WRKY genes were numbered according to their chromosomal location, and a complete revision of the numbering was performed. Amino acid variability between different cultivars was assessed for the first time and was greater than 5% for some WRKYs. According to the gene structure, all WRKYs could be divided into two groups: more exons/long length and fewer exons/short length. For the first time, some chimeric WRKY genes were found in grapevine, which may play a specific role in the regulation of different processes: VvWRKY17 (an N-terminal signal peptide region followed by a non-cytoplasmic domain) and VvWRKY61 (Frigida-like domain). Five phylogenetic clades A-E were revealed and correlated with the WRKY groups (I, II, III). The evolution of WRKY was studied, and we proposed a WRKY evolution model where there were two dynamic phases of complexity and simplification in the evolution of WRKY.

Genome-wide identification of bZIP transcription factors in 12 Rosaceae species and modeling of novel mechanisms of EjbZIPs response to salt stress.

In plantae, basic leucine zipper (bZIP) transcription factors (TFs) are widespread and regulate a variety of biological processes under abiotic stress. However, it has not been extensively studied in Rosaceae, and the functional effects of bZIP on Eriobotrya japonica under salt stress are still unknown. Therefore, in this study, the bZIP TF family of 12 species of Rosaceae was analyzed by bioinformatics method, and the expression profile and quantitative real-time polymerase chain reaction of E. japonica under salt stress were analyzed. The results showed that a total of 869 bZIP TFs were identified in 12 species of Rosaceae and divided into nine subfamilies. Differences in promoter cis-elements between subfamilies vary depending on their role. Species belonging to the same subfamily have a similar number of chromosomes and the number of genes contained on each chromosome. Gene duplication analysis has found segmental duplication to be a prime force in the evolution of Rosaceae species. In addition, nine EjbZIPs were significantly different, including seven up-regulated and two down-regulated in E. japonica under salt stress. Especially, EjbZIP13 was involved in the expression of SA-responsive proteins by binding to the NPR1 gene. EjbZIP27, EjbZIP30, and EjbZIP38 were highly expressed in E. japonica under salt stress, thus improving the salt tolerance capacity of the plants. These results can provide a theoretical basis for exploring the characteristics and functions of the bZIP TF family in more species and breeding salt-tolerant E. japonica varieties. It also provides a reference for resolving the response mechanism of bZIP TF in 12 Rosaceae species under salt stress.

Cancer-specific epigenome identifies oncogenic hijacking by nuclear factor I family proteins for medulloblastoma progression

Normal cells coordinate proliferation and differentiation by precise tuning of gene expression based on the dynamic shifts of the epigenome throughout the developmental timeline. Although non-mutational epigenetic reprogramming is an emerging hallmark of cancer, the epigenomic shifts that occur during the transition from normal to malignant cells remain elusive. Here, we capture the epigenomic changes that occur during tumorigenesis in a prototypic embryonal brain tumor, medulloblastoma. By comparing the epigenomes of the different stages of transforming cells in mice, we identify nuclear factor I family of transcription factors, known to be cell fate determinants in development, as oncogenic regulators in the epigenomes of precancerous and cancerous cells. Furthermore, genetic and pharmacological inhibition of NFIB validated a crucial role of this transcription factor by disrupting the cancer epigenome in medulloblastoma. Thus, this study exemplifies how epigenomic changes contribute to tumorigenesis via non-mutational mechanisms involving developmental transcription factors.

Genetic and Molecular Regulation of Cotton Fiber Initiation and Elongation

Cotton fiber, a crucial and sustainable resource for global textile production, undergoes a complex five-stage developmental process, encompassing initiation, elongation, transition, secondary cell wall biosynthesis, and maturation. These elongated single-cell fibers originate from the outer ovule epidermis. The development of cotton fibers involves intricate changes in gene expression and physiological processes, resulting in a nearly pure cellulose product that is vital for the global cotton industry. Decoding the genes associated with fiber development enhances our understanding of cotton fiber mechanisms and facilitates the cultivation of varieties with enhanced quality. In recent decades, advanced omics approaches, including genomics, transcriptomics, and proteomics, have played a pivotal role in identifying the genes and gene products linked to cotton fiber development, including the MYB transcription factor family, which coordinates cotton fiber development. Molecular studies have revealed the transcription factors, like MYB, WRKY, Homeodomain Leucine Zipper (HD-ZIP), and basic helix–loop–helix (bHLH), influencing fiber initiation and elongation. The intricate interplay of phytohormones, like auxin, gibberellic acid (GA), brassinosteroids (BRs), jasmonic acid (JA), ethylene, abscisic acid (ABA), and cytokinin, is explored, providing a comprehensive perspective on the shaping of cotton fibers. Numerous candidate genes and cellular processes affecting various aspects of fiber development hold promise for genetic engineering or marker-assisted breeding to improve fiber quality. This review presents a comprehensive overview of key achievements in cotton molecular biology, with a specific emphasis on recent advancements in understanding the transcription factors and phytohormones involved in cotton fiber initiation and elongation.

A first-in-human, phase 1/2 trial of FOG-001, a β-catenin:TCF antagonist, in patients with locally advanced or metastatic solid tumors.

TPS3175 Background: The Wnt/β-catenin pathway is a frequently activated oncogenic pathway and a well-described driver of many cancers. FOG-001 is designed to be a first-in-class direct inhibitor of β-catenin that blocks β-catenin’s interaction with the T-cell factor (TCF) family of transcription factors. Preclinical studies have indicated FOG-001 can cause tumor growth inhibition and regression by disrupting β-catenin-dependent signaling. FOG-001 is unique from previously reported Wnt/β-catenin pathway modulators as it is designed to directly inhibit TCF transcription factor and β-catenin interaction, the most downstream node in the Wnt pathway. It is hypothesized FOG-001 will abrogate the hyperactivation of the Wnt pathway that is driven by most known pathway mutations. Methods: This first-in-human, Phase 1/2, multicenter, open-label, dose escalation (Parts 1a and 1b) and dose-expansion (Part 2) study is evaluating the safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of FOG-001 in patients with advanced or metastatic solid tumors. Patients with the following tumor types are eligible: microsatellite stable (MSS) colorectal cancer (CRC) or any solid tumor with documented Wnt pathway activating mutation (WPAM) (Part 1a), MSS CRC only (Part 1b) and MSS CRC, gastric/gastroesophageal (GEJ) cancer, non-small cell lung cancer (NSCLC), and any solid tumors with documented WPAM in Part 2. Patients must have received ≥1 prior systemic anticancer therapy(ies) and be ineligible for curative surgery or curative chemoradiation. In Part 1, FOG-001 is administered at escalating doses via intravenous (IV) infusion on Days 1, 8, 15, and 22 of each 4-week cycle; additional dosing regimens may be explored. After selection of the preliminary recommended Phase 2 dose(s) (pRP2D) and regimen(s) in Part 1, the following cohorts will be enrolled to receive FOG-001 at the pRP2D in Part 2: (2a) MSS CRC; (2b) NSCLC with documented WPAM in adenomatous polyposis coli (APC) or β-catenin; (2c) gastric/GEJ cancer with documented WPAM in APC or β-catenin; and (2d) solid tumors with ≥1 documented WPAM in any predefined Wnt pathway genes. The primary endpoints are safety/tolerability (Parts 1 and 2), and also preliminary antitumor activity (objective response rate) (Part 2). Secondary endpoints are PK, PD, and additional antitumor activity assessments. Enrollment in Part 1 is ongoing. Clinical trial information: NCT05919264 .