Superfamily Of Transcription Factors Research Articles

Functional analysis of TkWRKY33: A key regulator in drought-induced natural rubber synthesis in Taraxacum kok-saghyz

WRKY proteins, which form a transcription factor superfamily that responds to jasmonic acid (JA) signals, regulate various developmental processes and stress responses in plants, including Taraxacum kok-saghyz (TKS). TKS serves as an ideal model plant for studying rubber production and lays the foundation for a comprehensive understanding of JA-mediated regulation of natural rubber synthesis. In the present study, we screened and identified a valuable transcription factor, TkWRKY33, based on transcriptome data from TKS in response to JA. We investigated its role in the regulation of natural rubber synthesis within the JA signaling pathway and its function in response to drought stress. Through protein-protein interactions and transcriptional regulation analysis, we found that TkWRKY33 may regulate natural rubber synthesis through the JA-TkMPK3-TkWRKY33-(TkGGPS5/TkACAT8) cascade pathway, possibly by participating in JA-activated mitogen-activated protein kinase (MAPK) signaling. Overexpression of TkWRKY33 in tobacco, along with functional analysis of drought resistance and comparative analysis of natural rubber content after drought stress, revealed that TkWRKY33 not only enhances plant drought resistance by regulating the expression of genes related to reactive oxygen species (ROS) scavenging through the JA signaling pathway, but also has a close relationship with the signal transduction pathway mediated by the JA hormone in regulating natural rubber synthesis.The TkWRKY33 is recognized as a valuable transcription factor, which likely plays a role in regulating natural rubber biosynthesis through the JA-activated MAPK cascade signaling pathway JA-TkMPK3-TkWRKY33-(TkGGPS5/TkACAT8).

The Role of Pea3 Transcription Factor Subfamily in the Nervous System.

ETS domain transcription factor superfamily is highly conserved throughout metazoa and is involved in many aspects of development and tissue morphogenesis, and as such, the deregulation of ETS proteins is quite common in many diseases, including cancer. The PEA3 subfamily in particular has been extensively studied with respect to tumorigenesis and metastasis; however, they are also involved in the development of many tissues with branching morphogenesis, such as lung or kidney development. In this review, we aim to summarize findings from various studies on the role of Pea3 subfamily members in nervous system development in the embryo, as well as their functions in the adult neurons. We further discuss the different signals that were shown to regulate the function of the Pea3 family and indicate how this signal-dependent regulation of Pea3 proteins can generate neuronal circuit specificity through unique gene regulation. Finally, we discuss how these developmental roles of Pea3 proteins relate to their role in tumorigenesis.

Targeting Liver X Receptors in Cancer Drug Discovery

Liver X receptors (LXRs) are members of the nuclear receptor superfamily of ligand-dependent transcription factors. LXRα is predominantly expressed in metabolic tissues, whereas LXRβ is ubiquitously expressed. Upon ligand binding, they regulate the expression of target genes involved in lipid metabolism, cholesterol homeostasis, and immune responses, including those which function in pathways that are commonly reprogrammed during carcinogenesis. Known LXR ligands include oxysterols and natural and synthetic agonists which upregulate LXR transcriptional activity and target gene expression. Synthetic inverse agonists have also been identified that inhibit LXR activity. While both types of ligands have been shown to inhibit cancer cells and tumor growth either directly or indirectly by modulating the activities of stromal cells within the tumor microenvironment, they appear to target different aspects of cancer metabolism and other cancer hallmarks, including immune evasion. This review summarizes the characterization of LXRs and their ligands and their mechanisms of action in cancer models and discusses the future directions for translating these discoveries into novel cancer therapeutics.

Functional annotation and meta-analysis of maize transcriptomes reveal genes involved in biotic and abiotic stress

BackgroundEnvironmental stress factors, such as biotic and abiotic stress, are becoming more common due to climate variability, significantly affecting global maize yield. Transcriptome profiling studies provide insights into the molecular mechanisms underlying stress response in maize, though the functions of many genes are still unknown. To enhance the functional annotation of maize-specific genes, MaizeGDB has outlined a data-driven approach with an emphasis on identifying genes and traits related to biotic and abiotic stress.ResultsWe mapped high-quality RNA-Seq expression reads from 24 different publicly available datasets (17 abiotic and seven biotic studies) generated from the B73 cultivar to the recent version of the reference genome B73 (B73v5) and deduced stress-related functional annotation of maize gene models. We conducted a robust meta-analysis of the transcriptome profiles from the datasets to identify maize loci responsive to stress, identifying 3,230 differentially expressed genes (DEGs): 2,555 DEGs regulated in response to abiotic stress, 408 DEGs regulated during biotic stress, and 267 common DEGs (co-DEGs) that overlap between abiotic and biotic stress. We discovered hub genes from network analyses, and among the hub genes of the co-DEGs we identified a putative NAC domain transcription factor superfamily protein (Zm00001eb369060) IDP275, which previously responded to herbivory and drought stress. IDP275 was up-regulated in our analysis in response to eight different abiotic and four different biotic stresses. A gene set enrichment and pathway analysis of hub genes of the co-DEGs revealed hormone-mediated signaling processes and phenylpropanoid biosynthesis pathways, respectively. Using phylostratigraphic analysis, we also demonstrated how abiotic and biotic stress genes differentially evolve to adapt to changing environments.ConclusionsThese results will help facilitate the functional annotation of multiple stress response gene models and annotation in maize. Data can be accessed and downloaded at the Maize Genetics and Genomics Database (MaizeGDB).

Genome-wide prediction and functional analysis of WOX genes in blueberry.

WOX genes are a class of plant-specific transcription factors. The WUSCHEL-related homeobox (WOX) family is a member of the homeobox transcription factor superfamily. Previous studies have shown that WOX members play important roles in plant growth and development. However, studies of the WOX gene family in blueberry plants have not been reported. In order to understand the biological function of the WOX gene family in blueberries, bioinformatics were used methods to identify WOX gene family members in the blueberry genome, and analyzed the basic physical and chemical properties, gene structure, gene motifs, promoter cis-acting elements, chromosome location, evolutionary relationships, expression pattern of these family members and predicted their functions. Finally, 12 genes containing the WOX domain were identified and found to be distributed on eight chromosomes. Phylogenetic tree analysis showed that the blueberry WOX gene family had three major branches: ancient branch, middle branch, and WUS branch. Blueberry WOX gene family protein sequences differ in amino acid number, molecular weight, isoelectric point and hydrophobicity. Predictive analysis of promoter cis-acting elements showed that the promoters of the VdWOX genes contained abundant light response, hormone, and stress response elements. The VdWOX genes were induced to express in both stems and leaves in response to salt and drought stress. Our results provided comprehensive characteristics of the WOX gene family and important clues for further exploration of its role in the growth, development and resistance to various stress in blueberry plants.

Elucidating the Transcriptional Role of the Nuclear Receptor RORα in CD8+ T Cell Memory vs Effector Cell Development

Abstract CD8+ T cells play a critical role in controlling viral infections and cancer and have the potential to be harnessed for the development of new therapeutic strategies. Defining the transcriptional regulatory networks that control CD8+ T cell differentiation and function is of great importance to achieve these goals. The retinoic acid receptor-related orphan receptor alpha (RORα), a member of the nuclear receptor superfamily of ligand-regulated transcription factors, has emerged as a potential transcriptional regulator of CD8+ T cell immunity. However, exactly how RORα functions in these processes is poorly understood. To this end we seek to identify the transcriptional role of RORα in regulating the differentiation of memory CD8+ T cells. Utilizing a mouse model with T cell-specific deletion of RORα we identify that RORα deficiency in CD8+ T cells leads to increased IFNγ production and increased cell-specific cytolytic function in vitro. Conversely, RORα overexpression results in decreased IFNγ production and defects in proliferative capacity in vitro. Our in vivo data further reveals that deletion of RORα in CD8+ T cells may affect the trafficking of these cells to non-lymphoid tissue and play a role in the development of tissue resident memory (TRM) cells. Our study provides important insights into the role of RORα in regulating CD8+ T cell function and highlights the potential for targeting nuclear receptors in the development of novel cell-based therapeutics.

Mitotic Kinases Aurora-A, Plk1, and Cdk1 Interact with Elk-1 Transcription Factor through the N-Terminal Domain.

Elk-1 is a member of the ETS domain transcription factor superfamily that is phosphorylated upon mitogen-activated protein kinase (MAPK) pathway activation, which in turn regulated its interaction with partner protein serum response factor (SRF), leading to formation of a ternary complex with DNA. It has previously been reported that Elk-1 interacts with a mitotic kinase Aurora-A, although the mechanisms or the relevance of this interaction was unclear. Elk-1 was also reported to be phosphorylated by CDK5 on Thr417 residue. In this study, we show for the first time that this transcription factor interacts not only with Aurora-A but also with other mitotic kinases Aurora-B, Plk1, and Cdk1, and we define the interaction domain on Elk-1 to the first N-terminal 205 amino acids. We also describe putative phosphorylation sites of these mitotic kinases on Elk-1 and show that Elk-1 peptides containing these residues get phosphorylated by the mitotic kinases in in vitro kinase assays. We also perform bioinformatic analysis of mitotic phosphoproteomes and determine potential interaction partners for Elk-1 in Plk or Aurora phosphoproteomes. We propose that understanding the dynamic phosphorylation of Elk-1 by mitotic kinases is important and that it can present a novel target for anticancer strategies.

Genome-Wide Analysis of MYB Gene Family in Chrysanthemum ×morifolium Provides Insights into Flower Color Regulation.

MYBs constitute the second largest transcription factor (TF) superfamily in flowering plants with substantial structural and functional diversity, which have been brought into focus because they affect flower colors by regulating anthocyanin biosynthesis. Up to now, the genomic data of several Chrysanthemum species have been released, which provides us with abundant genomic resources for revealing the evolution of the MYB gene family in Chrysanthemum species. In the present study, comparative analyses of the MYB gene family in six representative species, including C. lavandulifolium, C. seticuspe, C. ×morifolium, Helianthus annuus, Lactuca sativa, and Arabidopsis thaliana, were performed. A total of 1104 MYBs, which were classified into four subfamilies and 35 lineages, were identified in the three Chrysanthemum species (C. lavandulifolium, C. seticuspe, and C. ×morifolium). We found that whole-genome duplication and tandem duplication are the main duplication mechanisms that drove the occurrence of duplicates in CmMYBs (particularly in the R2R3-MYB subfamily) during the evolution of the cultivated chrysanthemums. Sequence structure and selective pressure analyses of the MYB gene family revealed that some of R2R3-MYBs were subjected to positive selection, which are mostly located on the distal telomere segments of the chromosomes and contain motifs 7 and 8. In addition, the gene expression analysis of CmMYBs in different organs and at various capitulum developmental stages of C. ×morifolium indicated that CmMYBS2, CmMYB96, and CmMYB109 might be the negative regulators for anthocyanin biosynthesis. Our results provide the phylogenetic context for research on the genetic and functional evolution of the MYB gene family in Chrysanthemum species and deepen our understanding of the regulatory mechanism of MYB TFs on the flower color of C. ×morifolium.

Escargot a Snail superfamily member and its multiple roles in Drosophila melanogaster development.

The Snail superfamily of transcription factors plays a crucial role in metazoan development; one of the most important vertebrate members of this family is Snai1 which is orthologous to the Drosophila melanogaster esg gene. This review offers a comprehensive examination of the roles of the esg gene in Drosophila development, covering its expression pattern and downstream targets, and draws parallels between the vertebrate Snai1 family proteins on controlling the epithelial-to-mesenchymal transition and esg. This gene regulates stemness, ploidy, and pluripontency. esg is expressed in various tissues during development, including the gut, imaginal discs, and neuroblasts. The functions of the esg include the suppression of differentiation in intestinal stem cells and the preservation of diploidy in imaginal cells. In the nervous system development, esg expression also inhibits neuroblast differentiation, thus regulating the number of neurons and the moment in development of neuronal differentiation. Loss of esg function results in diverse developmental defects, including defects in intestinal stem cell maintenance and differentiation, and alters imaginal disc and nervous system development. Expression levels of esg also play a role in regulating longevity and metabolism in adult stages. This review provides an overview of the current understanding of esg's developmental role, emphasizing cellular and tissue effects that arise from its loss of function. The insights gained may contribute to a better understanding of evolutionary conserved developmental mechanisms and certain metabolic diseases.

Truncated variants of thyroid hormone receptor beta display disease-inflicting malfunctioning at cellular level

Thyroid hormone receptor β (THRβ) is a member of the nuclear receptor superfamily of ligand-modulated transcription factors. Upon ligand binding, THRβ sequentially recruits the components of transcriptional machinery to modulate target gene expression. In addition to regulating diverse physiological processes, THRβ plays a crucial role in hypothalamus-pituitary-thyroid axis feedback regulation. Anomalies in THRβ gene/protein structure are associated with onset of diverse disease states. In this study, we investigated disease-inflicting truncated variants of THRβ using in-silico analysis and cell-based assays. We examined the THRβ truncated variants on multiple test parameters, including subcellular localization, ligand-receptor interactions, transcriptional functions, interaction with heterodimeric partner RXR, and receptor-chromatin interactions. Moreover, molecular dynamic simulation approaches predicted that shortened THRβ-LBD due to point mutations contributes proportionally to the loss of structural integrity and receptor stability. Deviant subcellular localization and compromised transcriptional function were apparent with these truncated variants. Present study shows that ‘mitotic bookmarking’ property of some THRβ variants is also affected. The study highlights that structural and conformational attributes of THRβ are necessary for normal receptor functioning, and any deviations may contribute to the underlying cause of the inflicted diseases. We anticipate that insights derived herein may contribute to improved mechanistic understanding to assess disease predisposition.

Genome-wide characterization and expression of Oryza sativa AP2 transcription factor genes associated with the metabolism of mesotrione

BackgroundThe APETALA2 (AP2) transcription factor (TF) superfamily, one of the largest gene families in plants, plays an essential role in regulating plant growth and their stress responses. However, the role of AP2 in rice under pesticide stress remains unclear. To investigate the characteristics and functions of the rice AP2 gene family under pesticide stress, the expression of 105 AP2-coding genes and 26 AP2 differentially expressed genes (DEGs) were identified in mesotrione (MTR)-treated rice transcriptome datasets.ResultsThree subfamilies of the AP2 gene family (AP2/ERF, RAV, and soloists) were identified using sequence alignment and phylogenetic analysis. Chromosome location analysis revealed that the 26 rice AP2 DEGs were unevenly distributed on 10 of the 12 rice chromosomes, and segmental duplication contributed to the expansion of Oryza sativa AP2 (OsAP2) gene family. Collinearity analyses demonstrated that rice AP2 genes displayed 16 orthologous gene pairs, and 12 and 26 orthologous gene pairs were shared of Arabidopsis and soybean, respectively. In addition, rice AP2 genes featured various gene structures, cis-elements, motif compositions, and conserved domains that allowed them to encode genes that elicit biotic and abiotic stress responses. An analysis of docking between MTR and six AP2 DEGs revealed amino acid residues involved in MTR binding. Quantitative reverse transcription–polymerase chain reaction verified that several AP2 genes were preferentially expressed during MTR-induced stress. The roles of OsAP2 proteins in MTR metabolism were further supported by protein–protein interaction network analysis, which illustrated how these proteins interact with target proteins.ConclusionThe initial findings of this study define the features of the OsAP2 superfamily and offer important tools for functional analyses of OsAP2 genes implicated in the metabolism of MTR.Graphical

Evolution of the WRKY Family in Angiosperms and Functional Diversity under Environmental Stress.

The transcription factor is an essential factor for regulating the responses of plants to external stimuli. The WRKY protein is a superfamily of plant transcription factors involved in response to various stresses (e.g., cold, heat, salt, drought, ions, pathogens, and insects). During angiosperm evolution, the number and function of WRKY transcription factors constantly change. After suffering from long-term environmental battering, plants of different evolutionary statuses ultimately retained different numbers of WRKY family members. The WRKY family of proteins is generally divided into three large categories of angiosperms, owing to their conserved domain and three-dimensional structures. The WRKY transcription factors mediate plant adaptation to various environments via participating in various biological pathways, such as ROS (reactive oxygen species) and hormone signaling pathways, further regulating plant enzyme systems, stomatal closure, and leaf shrinkage physiological responses. This article analyzed the evolution of the WRKY family in angiosperms and its functions in responding to various external environments, especially the function and evolution in Magnoliaceae plants. It helps to gain a deeper understanding of the evolution and functional diversity of the WRKY family and provides theoretical and experimental references for studying the molecular mechanisms of environmental stress.

Starvation resistance in the nematode Pristionchus pacificus requires a conserved supplementary nuclear receptor

Nuclear hormone receptors (NHRs) are a deeply-conserved superfamily of metazoan transcription factors, which fine-tune the expression of their regulatory target genes in response to a plethora of sensory inputs. In nematodes, NHRs underwent an explosive expansion and many species have hundreds of nhr genes, most of which remain functionally uncharacterized. However, recent studies have reported that two sister receptors, Ppa-NHR-1 and Ppa-NHR-40, are crucial regulators of feeding-structure morphogenesis in the diplogastrid model nematode Pristionchus pacificus. In the present study, we functionally characterize Ppa-NHR-10, the sister paralog of Ppa-NHR-1 and Ppa-NHR-40, aiming to reveal whether it too regulates aspects of feeding-structure development. We used CRISPR/CAS9-mediated mutagenesis to create small frameshift mutations of this nuclear receptor gene and applied a combination of geometric morphometrics and unsupervised clustering to characterize potential mutant phenotypes. However, we found that Ppa-nhr-10 mutants do not show aberrant feeding-structure morphologies. Instead, multiple RNA-seq experiments revealed that many of the target genes of this receptor are involved in lipid catabolic processes. We hypothesized that their mis-regulation could affect the survival of mutant worms during starvation, where lipid catabolism is often essential. Indeed, using novel survival assays, we found that mutant worms show drastically decreased starvation resistance, both as young adults and as dauer larvae. We also characterized genome-wide changes to the transcriptional landscape in P. pacificus when exposed to 24 h of acute starvation, and found that Ppa-NHR-10 partially regulates some of these responses. Taken together, these results demonstrate that Ppa-NHR-10 is broadly required for starvation resistance and regulates different biological processes than its closest paralogs Ppa-NHR-1 and Ppa-NHR-40.

The Prognostic and Immune Significance of BZW2 in Pan-Cancer and its Relationship with Proliferation and Apoptosis of Cervical Cancer.

Basic leucine zipper and W2 domains 2 (BZW2), a member of the basic domain leucine zipper superfamily of transcription factors, has been implicated in the development and progression of various cancers. However, the precise biological role of BZW2 in pan-cancer datasets remains to be explored. This study aimed to assess the prognostic significance of BZW2 and its immune-related signatures in various tumors. Our study investigated the expression, epigenetic modifications, and clinical prognostic relevance of BZW2 using multi-omics data in different cancer types. Additionally, the immunological characteristics, tumor stemness, drug sensitivity, and correlation of BZW2 with immunotherapy response were explored. Finally, in vitro experiments were conducted to assess the impact of BZW2 knockdown on Hela cells, a cell line derived from cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). BZW2 exhibited elevated expression levels in various tumor tissues and significantly impacted the prognosis of different cancer types. BZW2 emerged as an independent prognostic factor in CESC. We found that copy number amplification and methylation levels of BZW2 were associated with its mRNA expression. Immunological analyses revealed that BZW2 shapes a non-inflamed immunosuppressive tumor microenvironment across multiple cancers. Furthermore, our cell experiments demonstrated that BZW2 knockdown reduced proliferation, migration, and apoptosis activities in CESC cells. BZW2 promotes cancer progression by shaping a non-inflamed immunosuppressive tumor microenvironment. Additionally, BZW2 was shown to significantly influence the proliferation, migration, and apoptosis of CESC cells.

Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.

Recent advances have brought forth the complex interplay between tumor cell plasticity and its consequential impact on drug resistance and tumor recurrence, both of which are critical determinants of neoplastic progression and therapeutic efficacy. Various forms of tumor cell plasticity, instrumental in facilitating neoplastic cells to develop drug resistance, include epithelial-mesenchymal transition (EMT) alternatively termed epithelial-mesenchymal plasticity, the acquisition of cancer stem cell (CSC) attributes, and transdifferentiation into diverse cell lineages. Nuclear receptors (NRs) are a superfamily of transcription factors (TFs) that play an essential role in regulating a multitude of cellular processes, including cell proliferation,differentiation, and apoptosis. NRs have been implicated to play a critical role in modulating gene expression associated with tumor cell plasticity and drug resistance. This review aims to provide a comprehensive overview of the current understanding of how NRs regulate these key aspects of cancer biology. We discuss the diverse mechanisms through which NRs influence tumor cell plasticity, including EMT, stemness, and metastasis. Further, we explore the intricate relationship between NRs and drug resistance, highlighting the impact of NR signaling on chemotherapy, radiotherapy andtargeted therapies. We also discuss the emerging therapeutic strategies targeting NRs to overcome tumor cell plasticity and drug resistance. This review also provides valuable insights into the current clinical trials that involve agonists or antagonists of NRs modulating various aspects of tumor cell plasticity, thereby delineating the potential of NRs as therapeutic targets for improved cancer treatment outcomes.

Comprehensive analysis of B3 family genes in pearl millet (Pennisetum glaucum) and the negative regulator role of PgRAV-04 in drought tolerance.

Members of the plant-specific B3 transcription factor superfamily play crucial roles in various plant growth and developmental processes. Despite numerous valuable studies on B3 genes in other species, little is known about the B3 superfamily in pearl millet. Here, through comparative genomic analysis, we identified 70 B3 proteins in pearl millet and categorized them into four subfamilies based on phylogenetic affiliations: ARF, RAV, LAV, and REM. We also mapped the chromosomal locations of these proteins and analyzed their gene structures, conserved motifs, and gene duplication events, providing new insights into their potential functional interactions. Using transcriptomic sequencing and real-time quantitative PCR, we determined that most PgB3 genes exhibit upregulated expression under drought and high-temperature stresses, indicating their involvement in stress response regulation. To delve deeper into the abiotic stress roles of the B3 family, we focused on a specific gene within the RAV subfamily, PgRAV-04, cloning it and overexpressing it in tobacco. PgRAV-04 overexpression led to increased drought sensitivity in the transgenic plants due to decreased proline levels and peroxidase activity. This study not only adds to the existing body of knowledge on the B3 family's characteristics but also advances our functional understanding of the PgB3 genes in pearl millet, reinforcing the significance of these factors in stress adaptation mechanisms.

Cloning, Characterization, and Expression Pattern Analysis of the BBM Gene in Tree Peony (Paeonia ostii)

BABY BOOM (BBM) is one of the members of the plant-specific APETALA2/ethylene-responsive factor (AP2/ERF) transcription factor superfamily. It acts as a key regulator of plant cell pluripotency, playing a significant role in promoting somatic embryogenesis. In this study, a BBM gene named PoBBM was screened, cloned, and identified from the third-generation full-length transcriptome data of Paeonia ostii. Its open reading frame was 2136 bp, encoding 711 amino acids. Sequence feature analysis revealed that it possessed two AP2 conserved domains and eight motifs, including bbm-1. The phylogenetic tree indicated that PoBBM clusters with AtBBM in the euANT group of the Arabidopsis AP2 family, which is most closely related to grape VvBBM and may have the same ancestry as grape. Subcellular localization demonstrated that the PoBBM protein was localized in the nucleus. Semi-quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess the PoBBM transcript levels during ten developmental stages of somatic embryos and in five tissue types of peonies. The results indicate that PoBBM was highly expressed in the early stages of peony somatic embryo development. The expression on 0–15 d was the highest and decreased gradually with somatic embryogenesis. The gene is almost not expressed after 40 d since somatic embryo formation. PoBBM was expressed in roots, stems, leaves, seeds, and calli, with the highest levels in seeds, followed by leaves and calli. The PoBBM protein displayed transcriptional self-activation activity, which may facilitate further research on its relationships with other proteins. The above results provide a key gene PoBBM for somatic embryogenesis in peonies, which is significant for advancing the establishment of a stable and efficient regeneration and genetic transformation system for peonies.

ERRα: unraveling its role as a key player in cell migration.

Cell migration is essential throughout the life of multicellular organisms, and largely depends on the spatial and temporal regulation of cytoskeletal dynamics, cell adhesion and signal transduction. Interestingly, Estrogen-related receptor alpha (ERRα) has been identified as a major regulator of cell migration in both physiological and pathological conditions. ERRα is an orphan member of the nuclear hormone receptor superfamily of transcription factors and displays many biological functions. ERRα is a global regulator of energy metabolism, and it is also highly involved in bone homeostasis, development, differentiation, immunity and cancer progression. Importantly, in some instances, the regulation of these biological processes relies on the ability to orchestrate cell movements. Therefore, this review describes how ERRα-mediated cell migration contributes not only to tissue homeostasis but also to tumorigenesis and metastasis, and highlights the molecular and cellular mechanisms by which ERRα finely controls the cell migratory potential.

Differential spatial distribution of HNF4α isoforms during dysplastic progression of intraductal papillary mucinous neoplasms of the pancreas

Hepatocyte Nuclear Factor 4-alpha (HNF4α) comprises a nuclear receptor superfamily of ligand-dependent transcription factors that yields twelve isoforms in humans, classified into promoters P1 or P2-associated groups with specific functions. Alterations in HNF4α isoforms have been associated with tumorigenesis. However, the distribution of its isoforms during progression from dysplasia to malignancy has not been studied, nor has it yet been studied in intraductal papillary mucinous neoplasms, where both malignant and pre-malignant forms are routinely clinically identified. We examined the expression patterns of pan-promoter, P1-specific, and P2-specific isoform groups in normal pancreatic components and IPMNs. Pan-promoter, P1 and P2 nuclear expression were weakly positive in normal pancreatic components. Nuclear expression for all isoform groups was increased in low-grade IPMN, high-grade IPMN, and well-differentiated invasive adenocarcinoma. Poorly differentiated invasive components in IPMNs showed loss of all forms of HNF4α. Pan-promoter, and P1-specific HNF4α expression showed shifts in subnuclear and sub-anatomical distribution in IPMN, whereas P2 expression was consistently nuclear. Tumor cells with high-grade dysplasia at the basal interface with the stroma showed reduced expression of P1, while P2 was equally expressed in both components. Additional functional studies are warranted to further explore the mechanisms underlying the spatial and differential distribution of HNF4α isoforms in IPMNs.

Exploration of the B3 transcription factor superfamily in Aquilaria sinensis reveal their involvement in seed recalcitrance and agarwood formation.

The endangered tree species of the Aquilaria genus produce agarwood, a high value material produced only after wounding; however, conservation of Aquilaria seeds is difficult. The B3 transcription factor family has diverse important functions in plant development, especially in seed development, although their functions in other areas, such as stress responses, remain to be revealed. Here germination tests proved that the seeds of A. sinensis were recalcitrant seeds. To provide insights into the B3 superfamily, the members were identified and characterized by bioinformatic approaches and classified by phylogenetic analysis and domain structure. In total, 71 members were identified and classified into four subfamilies. Each subfamily not only had similar domains, but also had conserved motifs in their B3 domains. For the seed-related LAV subfamily, the B3 domain of AsLAV3 was identical to that of AsVALs but lacked a typical zf-CW domain such as VALs. AsLAV5 lacks a typical PHD-L domain present in Arabidopsis VALs. qRT-PCR expression analysis showed that the LEC2 ortholog AsLAV4 was not expressed in seeds. RAVs and REMs induced after wound treatment were also identified. These findings provide insights into the functions of B3 genes and seed recalcitrance of A. sinensis and indicate the role of B3 genes in wound response and agarwood formation.This is the first work to investigate the B3 family in A. sinensis and to provide insights of the molecular mechanism of seed recalcitrance.This will be a valuable guidance for studies of B3 genes in stress responses, secondary metabolite biosynthesis, and seed development.