The ancient Z-DNA and Z-RNA specific Zα fold has evolved modern roles in immunity and transcription through the natural selection of flipons.

The Zα fold specifically binds to both Z-DNA and Z-RNA, left-handed nucleic acid structures that form under physiological conditions and are encoded by flipons. I trace the Zα fold back to unicellular organisms representing all three domains of life and to the realm of giant nucleocytoplasmic DNA viruses (NCVs). The canonical Zα fold is present in the earliest known holozoan unicellular symbiont Capsaspora owczarzaki and persists in vertebrates and some invertebrates, but not in plants or fungi. In metazoans, starting with porifera, Zα is incorporated into the double-stranded RNA editing enzyme ADAR and reflects an early symbiont relationship with NCV. In vertebrates, Zα is also present in ZBP1 and PKZ proteins that recognize host-derived Z-RNAs to defend against modern-day viruses. A related Zα fold, also likely to bind Z-DNA, is present in proteins thought to modulate gene expression, including a subset of prokaryote arsR proteins and the p15 (PC4) family present in algae. Other Zα variants that probably play a more general role in the reinitiation of transcription include the archaeal and human transcription factor E and the human RNA polymerase 3 subunit C proteins. The roles in immunity and transcription underlie the natural selection of flipons.

Discovery of candidate genes involved in ethylene biosynthesis and signal transduction pathways related to peach bud cold resistance.

Background: Low temperature pose significant challenges to peach cultivation, causing severe damage to peach buds and restricting production and distribution. Ethylene, an important phytohormone, plays a critical role in enhancing plant cold resistance. Structural genes and transcription factors involved in ethylene biosynthesis and signal transduction pathways are associated with cold resistance. However, no research has specifically addressed their roles in peach cold resistance. Methods: In this study, we aimed for cold-resistance gene discovery in cold-sensitive peach cultivar "21Shiji" (21SJ) and cold-resistance cultivar "Shijizhixing" (SJZX) using RNA-seq and gas chromatography. Results: The findings revealed that under cold stress conditions, ethylene biosynthesis in "SJZX" was significantly induced. Subsequently, a structural gene, PpACO1-1, involved in ethylene biosynthesis in peach buds was significantly upregulated and showed a higher correlation with ethylene release rate. To identify potential transcription factors associated with PpACO1-1 expression and ethylene signal transduction, weighted gene co-expression network analysis was conducted using RNA-seq data. Four transcription factors: PpERF2, PpNAC078, PpWRKY65 and PpbHLH112, were identified. Conclusion: These findings provide valuable theoretical insights for investigating the regulatory mechanisms of peach cold resistance and guiding breeding strategies.

De novo transcriptome analysis identifies RpMYB1 as an activator of anthocyanin biosynthesis in Rehmannia piasezkii.

Rehmannia piasezkii is a kind of medicinal plants, of the Orobanchaceae family, and well known for its large pink or purple corolla. However, no research on the molecular mechanism of flower color formation in R. piasezkii has been conducted so far. In this study, we investigated the transcriptome of root, stem, leaf and corollas of R. piasezkii using transcriptome sequencing technology and assembled 144,582 unigenes. A total of 58 anthocyanin biosynthetic genes were identified in the R. piasezkii transcriptome, fourteen of which were highly correlated with anthocyanin content, especially RpF3H2, RpDFR2, RpANS1, RpANS2 and RpUFGT. Totally, 35 MYB genes with FPKM values greater than 5 were identified in the R. piasezkii transcriptome, including an R2R3 MYB transcriptional factor RpMYB1, which belongs to subgroup 6 of the R2R3 MYB family. Agrobacterium-mediated transient expression of Nicotiana benthamiana revealed that overexpression of RpMYB1 could activate the expression of structural genes in anthocyanin synthesis pathway and promote the accumulation of anthocyanins in N. benthamiana leaves, indicating that RpMYB1 is a positive regulator of anthocyanin synthesis. Furthermore, combined transient overexpression of RpMYB1 with RpANS1, RpMYB1+RpANS1 with other structural genes all could further enhance the accumulation of anthocyanins in N. benthamiana leaves. Permanent overexpression of RpMYB1 in R. glutinosa promoted anthocyanin accumulation and expression levels of RgCHS, RgF3H, RgDFR and RgANS. Further evidence from dual-luciferase assay suggested that RpMYB1 could bind to the promoter of RpDFR2 and hence activating its expression. These findings provide insight into the molecular regulation in anthocyanin biosynthesis in R. piasezkii and provide valuable genetic resources for the genetic improvement of flower color.

Gene Regulatory Network Analysis of Decidual Stromal Cells and Natural Killer Cells.

Human reproductive success relies on the proper differentiation of the uterine endometrium to facilitate implantation, formation of the placenta, and pregnancy. This process involves two critical types of decidual uterine cells: endometrial/decidual stromal cells (dS) and uterine/decidual natural killer (dNK) cells. To better understand the transcription factors governing the in vivo functions of these cells, we analyzed single-cell transcriptomics data from first-trimester terminations of pregnancy, and for the first time conducted gene regulatory network analysis of dS and dNK cell subpopulations. Our analysis revealed stromal cell populations that corresponded to previously described in vitro decidualized cells and senescent decidual cells. We discovered new decidualization driving transcription factors of stromal cells for early pregnancy, including DDIT3 and BRF2, which regulate oxidative stress protection. For dNK cells, we identified transcription factors involved in the immunotolerant (dNK1) subpopulation, including IRX3 and RELB, which repress the NFKB pathway. In contrast, for the less immunotolerant (dNK3) population we predicted TBX21 (T-bet) and IRF2-mediated upregulation of the interferon pathway. To determine the clinical relevance of our findings, we tested the overrepresentation of the predicted transcription factors target genes among cell type-specific regulated genes from pregnancy disorders, such as recurrent pregnancy loss and preeclampsia. We observed that the predicted decidualized stromal and dNK1-specific transcription factor target genes were enriched with the genes downregulated in pregnancy disorders, whereas the predicted dNK3-specific targets were enriched with genes upregulated in pregnancy disorders. Our findings emphasize the importance of stress tolerance pathways in stromal cell decidualization and immunotolerance promoting regulators in dNK differentiation.

Testing the Significance of Ranked Gene Sets in Genome-wide Transcriptome Profiling Data Using Weighted Rank Correlation Statistics.

Background: Popular gene set enrichment analysis approaches assumed that genes in the gene set contributed to the statistics equally. However, the genes in the transcription factors (TFs) derived gene sets, or gene sets constructed by TF targets identified by the ChIP-Seq experiment, have a rank attribute, as each of these genes have been assigned with a p-value which indicates the true or false possibilities of the ownerships of the genes belong to the gene sets. Objectives: Ignoring the rank information during the enrichment analysis will lead to improper statistical inference. We address this issue by developing of new method to test the significance of ranked gene sets in genome-wide transcriptome profiling data. Methods: A method was proposed by first creating ranked gene sets and gene lists and then applying weighted Kendall's tau rank correlation statistics to the test. After introducing top-down weights to the genes in the gene set, a new software called "Flaver" was developed. Results: Theoretical properties of the proposed method were established, and its differences over the GSEA approach were demonstrated when analyzing the transcriptome profiling data across 55 human tissues and 176 human cell-lines. The results indicated that the TFs identified by our method have higher tendency to be differentially expressed across the tissues analyzed than its competitors. It significantly outperforms the well-known gene set enrichment analyzing tools, GOStats (9%) and GSEA (17%), in analyzing well-documented human RNA transcriptome datasets. Conclusions: The method is outstanding in detecting gene sets of which the gene ranks were correlated with the expression levels of the genes in the transcriptome data.

Super-enhancer omics in stem cell.

The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of "super-enhancer omics", inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.

CREB-regulated transcription during glycogen synthesis in astrocytes.

Glycogen storage, conversion and utilization in astrocytes play an important role in brain energy metabolism. The conversion of glycogen to lactate through glycolysis occurs through the coordinated activities of various enzymes and inhibition of this process can impair different brain processes including formation of long-lasting memories. To replenish depleted glycogen stores, astrocytes undergo glycogen synthesis, a cellular process that has been shown to require transcription and translation during specific stimulation paradigms. However, the detail nuclear signaling mechanisms and transcriptional regulation during glycogen synthesis in astrocytes remains to be explored. In this report, we study the molecular mechanisms of vasoactive intestinal peptide (VIP)-induced glycogen synthesis in astrocytes. VIP is a potent neuropeptide that triggers glycogenolysis followed by glycogen synthesis in astrocytes. We show evidence that VIP-induced glycogen synthesis requires CREB-mediated transcription that is calcium dependent and requires conventional Protein Kinase C but not Protein Kinase A. In parallel to CREB activation, we demonstrate that VIP also triggers nuclear accumulation of the CREB coactivator CRTC2 in astrocytic nuclei. Transcriptome profiles of VIP-induced astrocytes identified robust CREB transcription, including a subset of genes linked to glucose and glycogen metabolism. Finally, we demonstrate that VIP-induced glycogen synthesis shares similar as well as distinct molecular signatures with glucose-induced glycogen synthesis, including the requirement of CREB-mediated transcription. Overall, our data demonstrates the importance of CREB-mediated transcription in astrocytes during stimulus-driven glycogenesis.

Targeting the RUNX3-miR-186-3p-DAT-IGF1R axis as a therapeutic strategy in a Parkinson's disease model.

With the increasing age of the population worldwide, the incidence rate of Parkinson's disease (PD) is increasing annually. Currently, the treatment strategy for PD only improves clinical symptoms. No effective treatment strategy can slow down the progression of the disease. In the present study, whole transcriptome sequencing was used to obtain the mRNA and miRNA expression profiles in a PD mouse model, which revealed the pathogenesis of PD. The transcription factor RUNX3 upregulated the miR-186-3p expression in the PD model. Furthermore, the high miR-186-3p expression in PD can be targeted to inhibit the DAT expression, resulting in a decrease in the dopamine content of dopaminergic neurons. Moreover, miR-186-3p can be targeted to inhibit the IGF1R expression and prevent the activation of the IGF1R-P-PI3K-P-AKT pathway, thus increasing the apoptosis of dopaminergic neurons by regulating the cytochrome c-Bax-cleaved caspase-3 pathway. Our research showed that the RUNX3-miR-186-3p-DAT-IGF1R axis plays a key role in the pathogenesis of PD, and miR-186-3p is a potential target for the treatment of PD.

The roles of E2F7 in cancer: Current knowledge and future prospects.

Background: E2F7 is a recently discovered member of the E2F family. Investigating the function and mechanism of E2F7 in the growth of tumors is significant for the clinical diagnosis and therapy of these malignancies. Objective: The purpose of this review is to provide theoretical basis for the diagnosis and treatment of malignant tumors by exploring E2F7. Methods: The relevant information was collected through the PubMed database using keyword searches "E2F7" and "cancer". Results: On the one hand, E2F7 plays an essential role in embryonic development, angiogenesis, and the nervous system. On the other hand, E2F7 is also linked to the occurrence and growth of various malignant tumors. Conclusion: E2F7 has potential as a therapeutic target in future cancer treatments.

Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity.

The master transcription factor of regulatory T (Treg) cells, forkhead box protein P3 (Foxp3), controls Treg cell function by targeting certain genes for activation or repression, but the specific mechanisms by which it mediates this activation or repression under different conditions remain unclear. We found that Ikzf1 associates with Foxp3 via its exon 5 (IkE5) and that IkE5-deficient Treg cells highly expressed genes that would otherwise be repressed by Foxp3 upon T cell receptor stimulation, including Ifng. Treg-specific IkE5-deletion caused interferon-γ (IFN-γ) overproduction, which destabilized Foxp3 expression and impaired Treg suppressive function, leading to systemic autoimmune disease and strong anti-tumor immunity. Pomalidomide, which degrades IKZF1 and IKZF3, induced IFN-γ overproduction in human Treg cells. Mechanistically, the Foxp3-Ikzf1-Ikzf3 complex competed with epigenetic co-activators, such as p300, for binding to target gene loci via chromatin remodeling. Therefore, the Ikzf1 association with Foxp3 is essential for the gene-repressive function of Foxp3 and could be exploited to treat autoimmune disease and cancer.

Long non-coding RNA NEAT1 induced by BHLHE40 activates Wnt/ß-catenin signaling and potentiates colorectal cancer progression.

BACKGROUND: Nuclear-enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), has been implicated in the colorectal cancer (CRC) progression. However, its upstream mechanism has not been well studied. In the present study, the functions and mechanisms of NEAT1 in CRC were investigated. METHODS: The NEAT1 expression in CRC tissues and CRC cells was analyzed by RT-qPCR. The genes co-expressed with NEAT1 in CRC were obtained from UALCAN, which were intersected with the transcription factors targeting NEAT1 from hTFtarget. Dual-luciferase assay, RT-qPCR, and ChIP were conducted to analyze the transcriptional regulatory relationship between BHLHE40 and NEAT1. LoVo and HCT-15 cells knocking down BHLHE40 and overexpressing NEAT1 were subjected to MTT, Transwell, Western blot, and flow cytometry to examine the malignant aggressiveness of CRC cells. The effects of knocking down BHLHE40 and overexpressing NEAT1 on tumor and lung metastasis were investigated in mice using HE and immunohistochemical analyses. RESULTS: NEAT1 and BHLHE40 were significantly overexpressed in CRC tissues and cells. BHLHE40 has a binding relationship with the NEAT1 promoter. Knockdown of BHLHE40 resulted in a reverted malignant phenotype in vitro and slowed tumor growth and metastasis dissemination in vivo, which were reversed by NEAT1 overexpression. Overexpression of BHLHE40 increased Wnt/ß-catenin pathway activity, but knockdown of NEAT1 decreased Wnt/ß-catenin pathway activity. CONCLUSIONS: BHLHE40 mediates the transcriptional activation of NEAT1, which activates the Wnt/ß-catenin pathway and promotes the CRC progression.

The characteristic analysis of TaTDF1 reveals its function related to male sterility in wheat (Triticum aestivum L.).

BACKGROUND: The male sterile lines are an important foundation for heterosis utilization in wheat (Triticum aestivum L.). Thereinto, pollen development is one of the indispensable processes of wheat reproductive development, and its fertility plays an important role in wheat heterosis utilization, and are usually influencing by genes. However, these key genes and their regulatory networks during pollen abortion are poorly understood in wheat. RESULTS: DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1) is a member of the R2R3-MYB family and has been shown to be essential for early tapetal layer development and pollen grain fertility in rice (Oryza sativa L.) and Arabidopsis thaliana. In order to clarify the function of TDF1 in wheat anthers development, we used OsTDF1 gene as a reference sequence and homologous cloned wheat TaTDF1 gene. TaTDF1 is localized in the nucleus. The average bolting time of Arabidopsis thaliana overexpressed strain (TaTDF1-OE) was 33 d, and its anther could be colored normally by Alexander staining solution, showing red. The dominant Mosaic suppression silence-line (TaTDF1-EAR) was blue-green in color, and the anthers were shrimpy and thin. The TaTDF1 interacting protein (TaMAP65) was confirmed using Yeast Two-Hybrid Assay (Y2H) and Bimolecular-Fluorescence Complementation (BiFC) experiments. The results showed that downregulated expression of TaTDF1 and TaMAP65 could cause anthers to be smaller and shrunken, leading to pollen abortion in TaTDF1 wheat plants induced by virus-induced gene-silencing technology. The expression pattern of TaTDF1 was influenced by TaMAP65. CONCLUSIONS: Thus, systematically revealing the regulatory mechanism of wheat TaTDF1 during anther and pollen grain development may provide new information on the molecular mechanism of pollen abortion in wheat.

FInCH: FIJI plugin for automated and scalable whole-image analysis of protein expression and cell morphology.

Study of morphogenesis and its regulation requires analytical tools that enable simultaneous assessment of processes operating at cellular level, such as synthesis of transcription factors (TF), with their effects at the tissue scale. Most current studies conduct histological, cellular and immunochemical (IHC) analyses in separate steps, introducing inevitable biases in finding and alignment of areas of interest at vastly distinct scales of organization, as well as image distortion associated with image repositioning or file modifications. These problems are particularly severe for longitudinal analyses of growing structures that change size and shape. Here we introduce a python-based application for automated and complete whole-slide measurement of expression of multiple TFs and associated cellular morphology. The plugin collects data at customizable scale from the cell-level to the entire structure, records each data point with positional information, accounts for ontogenetic transformation of structures and variation in slide positioning with scalable grid, and includes a customizable file manager that outputs collected data in association with full details of image classification (e.g., ontogenetic stage, population, IHC assay). We demonstrate the utility and accuracy of this application by automated measurement of morphology and associated expression of eight TFs for more than six million cells recorded with full positional information in beak tissues across 12 developmental stages and 25 study populations of a wild passerine bird. Our script is freely available as an open-source Fiji plugin and can be applied to IHC slides from any imaging platforms and transcriptional factors.

NEUROD1: transcriptional and epigenetic regulator of human and mouse neuronal and endocrine cell lineage programs.

Transcription factors belonging to the basic helix-loop-helix (bHLH) family are key regulators of cell fate specification and differentiation during development. Their dysregulation is implicated not only in developmental abnormalities but also in various adult diseases and cancers. Recently, the abilities of bHLH factors have been exploited in reprogramming strategies for cell replacement therapy. One such factor is NEUROD1, which has been associated with the reprogramming of the epigenetic landscape and potentially possessing pioneer factor abilities, initiating neuronal developmental programs, and enforcing pancreatic endocrine differentiation. The review aims to consolidate current knowledge on NEUROD1's multifaceted roles and mechanistic pathways in human and mouse cell differentiation and reprogramming, exploring NEUROD1 roles in guiding the development and reprogramming of neuroendocrine cell lineages. The review focuses on NEUROD1's molecular mechanisms, its interactions with other transcription factors, its role as a pioneer factor in chromatin remodeling, and its potential in cell reprogramming. We also show a differential potential of NEUROD1 in differentiation of neurons and pancreatic endocrine cells, highlighting its therapeutic potential and the necessity for further research to fully understand and utilize its capabilities.

Overexpression of ZlMYB1 and ZlMYB2 increases flavonoid contents and antioxidant capacity and enhances the inhibition of α-glucosidase and tyrosinase activity in rice seeds.

Anthocyanins are natural flavonoids with a high antioxidant power and many associated health benefits, but most rice produce little amounts of these compounds. In this study, 141 MYB transcription factors in 15 chromosomes, including the nucleus-localised ZlMYB1 (Zla03G003370) and ZlMYB2 (Zla15G015220), were discovered in Zizania latifolia. Overexpression of ZlMYB1 or ZlMYB2 in rice seeds induced black pericarps, and flavonoid content, antioxidant capacity, and α-glucosidase and tyrosinase inhibition effects significantly increased compared to those in the control seeds. ZlMYB1 and ZlMYB2 overexpression induced the upregulation of 764 and 279 genes, respectively, and the upregulation of 162 and 157 flavonoids, respectively, linked to a black pericarp phenotype. The expression of flavonoid 3'-hydroxylase and UDP-glycose flavonoid glycosyltransferase, as well as the activities of these enzymes, increased significantly in response to ZlMYB1 or ZlMYB2 overexpression. This study systematically confirmed that the overexpression of ZlMYB1 and ZlMYB2 promotes flavonoid biosynthesis (especially of anthocyanins) in rice.

The pineapple reference genome: Telomere-to-telomere assembly, manually curated annotation, and comparative analysis.

Pineapple is the third most crucial tropical fruit worldwide and available in five varieties. Genomes of different pineapple varieties have been released to date; however, none of them are complete, with all exhibiting substantial gaps and representing only two of the five pineapple varieties. This significantly hinders the advancement of pineapple breeding efforts. In this study, we sequenced the genomes of three varieties: a wild pineapple variety, a fiber pineapple variety, and a globally cultivated edible pineapple variety. We constructed the first gap-free reference genome (Ref) for pineapple. By consolidating multiple sources of evidence and manually revising each gene structure annotation, we identified 26,656 protein-coding genes. The BUSCO evaluation indicated a completeness of 99.2%, demonstrating the high quality of the gene structure annotations in this genome. Utilizing these resources, we identified 7,209 structural variations across the three varieties. Approximately 30.8% of pineapple genes were located within ±5 kb of structural variations, including 30 genes associated with anthocyanin synthesis. Further analysis and functional experiments demonstrated that the high expression of AcMYB528 aligns with the accumulation of anthocyanins in the leaves, both of which may be affected by a 1.9-kb insertion fragment. In addition, we developed the Ananas Genome Database, which offers data browsing, retrieval, analysis, and download functions. The construction of this database addresses the lack of pineapple genome resource databases. In summary, we acquired a seamless pineapple reference genome with high-quality gene structure annotations, providing a solid foundation for pineapple genomics and a valuable reference for pineapple breeding.

Cancer, metastasis, and the epigenome.

Cancer is the second leading cause of death worldwide and disease burden is expected to increase globally throughout the next several decades, with the majority of cancer-related deaths occurring in metastatic disease. Cancers exhibit known hallmarks that endow them with increased survival and proliferative capacities, frequently as a result of de-stabilizing mutations. However, the genomic features that resolve metastatic clones from primary tumors are not yet well-characterized, as no mutational landscape has been identified as predictive of metastasis. Further, many cancers exhibit no known mutation signature. This suggests a larger role for non-mutational genome re-organization in promoting cancer evolution and dissemination. In this review, we highlight current critical needs for understanding cell state transitions and clonal selection advantages for metastatic cancer cells. We examine links between epigenetic states, genome structure, and misregulation of tumor suppressors and oncogenes, and discuss how recent technologies for understanding domain-scale regulation have been leveraged for a more complete picture of oncogenic and metastatic potential.

Exploring SALL4 as a significant prognostic marker in breast cancer and its association with progression pathways involved in cancer genesis.

Breast carcinoma is the leading factor in women's cancer-related fatalities. Due to its numerous inherent molecular subtypes, breast cancer is an extremely diverse illness. The human epidermal growth factor receptor 2 (HER2) positive subtypes stands out among these subtypes as being especially prone to cancer development and illness recurrence. The regulation of embryonic stem cells' pluripotency and self-renewal is carried out by the SALL4 (Spalt-like transcription factor 4) family member. Numerous molecular pathways operating at the transcriptional, post-transcriptional, and epigenomic levels regulate the expression of SALL4. Many transcription factors control the expression of SALL4, with STAT3 being the primary regulator in hepatocellular carcinoma (HCC) and breast carcinoma. Moreover, this oncogene has been connected to a number of cellular functions, including invasion, apoptosis, proliferation, and resistance to therapy. Reduced patient survival rates and a worse prognosis have been linked to higher levels of SALL4. In order to target the undruggable SALL4 that is overexpressed in breast carcinoma, we investigated the prognostic levels of SALL4 in breast carcinoma and its interaction with various related proteins. Using TIMER 2.0 analysis, the expression pattern of SALL4 was investigated across all TCGA datasets. The research revealed that SALL4 expression was elevated in various cancers. The UALCAN findings demonstrated that SALL4 was overexpressed in all tumor samples including breast cancer especially TNBC (Triple negative breast cancer). The web-based ENRICHR program was used for gene ontology analysis that revealed SALL4 was actively involved in the development of the nervous system, positive regulation of stem cell proliferation, regulation of stem cell proliferation, regulation of the activin receptor signaling pathway, regulation of transcription using DNA templates, miRNA metabolic processes, and regulation of transcription by RNA Polymerase I. Using the STRING database, we analyzed the interaction and involvement of SALL4 with other abruptly activated proteins and used Cytoscape 3.8.0 for visualization. Additionally, using bc-GenExMiner, we studied the impact of SALL4 on pathways abruptly activated in different breast cancer subtypes that revealed SALL4 was highly correlated with WNT2B, NOTCH4, AKT3, and PIK3CA. Furthermore, to target SALL4, we evaluated and analyzed the impact of CLP and its analogues, revealing promising outcomes.

[Identification and expression pattern analysis of Trihelix transcription factor family genes of ginseng].

The function of the Trihelix transcription factor is that it plays an important role in many abiotic stresses, especially in the signaling pathway of low temperature, drought, flood, saline, abscisic acid, methyl jasmonate, and other abiotic stresses. However, there are few studies on the Trihelix gene family of ginseng. In this study, 41 Trihelix gene family members were identified and screened from the ginseng genome database, and their physicochemical properties, cis-acting elements, subcellular localization, chromosomal assignment, and abiotic stress-induced expression patterns were analyzed by bioinformatics methods. The results showed that 85% of Trihelix family members of ginseng were located in the nucleus, and the main secondary structure of Trihelix protein was random coil and α helix. In the promoter region of Trihelix, cis-acting regulatory elements related to various abiotic stresses such as low temperature, hormone response, and growth and development were identified. Through the collinearity analysis of interspecific Trihelix transcription factors of model plants Arabidopsis thaliana and ginseng, 19 collinear gene pairs were found between A. thaliana and ginseng, and no collinear gene pairs existed on chromosomes 3, 6, and 12 only. qRT-PCR analysis showed that the expression of GWHGBEIJ010320.1 was significantly up-regulated under low temperature stress, a significant response to low temperature stress. This study lays a foundation for further research on the role of the Trihelix transcription factor of ginseng in abiotic stress, as well as the growth and development of ginseng.

Six1 Regulates Mouse Incisor Development by Promoting Dlx1/2/5 Expression.

Tooth development is a complex process orchestrated by intricate gene regulatory networks, involving both odontogenic epithelium and ectomesenchyme. Six1, a pivotal transcription factor (TF), is involved in the development of the lower incisor. However, its precise role during incisor development and the molecular mechanisms underpinning its regulatory functions remain poorly understood. This study employs Six1 deletion mouse models to elucidate the critical regulatory role of Six1 in governing dental mesenchyme development. By performing single-cell RNA sequencing, we constructed a comprehensive transcriptome atlas of tooth germ development from the bud to bell stage. Our analyses suggest that the dental follicle and the dental papilla (DP) are differentiated from dental ectomesenchyme (DEM) and identify the key TFs underlying these distinct states. Notably, we show that Dlx1, Dlx2, and Dlx5 (Dlx1/2/5) may function as the key TFs that promote the formation of DP. We further show that the deletion of Six1 perturbs dental mesenchyme development by impeding the transitions from DEM to DP states. Importantly, SIX1 directly binds to the promoters of Dlx1/2/5 to promote their co-expression, which subsequently leads to widespread epigenetic and transcriptional remodeling. In summary, our findings unveil Six1's indispensable role in incisor development, offering key insights into TF-driven regulatory networks that govern dental mesenchyme cell fate transitions during tooth development.