Homeobox Transcription Factor Research Articles

An activity-regulated transcriptional program directly drives synaptogenesis.

Although the molecular composition and architecture of synapses have been widely explored, much less is known about what genetic programs directly activate synaptic gene expression and how they are modulated. Here, using Caenorhabditis elegans dopaminergic neurons, we reveal that EGL-43/MECOM and FOS-1/FOS control an activity-dependent synaptogenesis program. Loss of either factor severely reduces presynaptic protein expression. Both factors bind directly to promoters of synaptic genes and act together with CUT homeobox transcription factors to activate transcription. egl-43 and fos-1 mutually promote each other's expression, and increasing the binding affinity of FOS-1 to the egl-43 locus results in increased presynaptic protein expression and synaptic function. EGL-43 regulates the expression of multiple transcription factors, including activity-regulated factors and developmental factors that define multiple aspects of dopaminergic identity. Together, we describe a robust genetic program underlying activity-regulated synapse formation during development.

Knockdown of CDX2 Induces microRNA-221 Up-regulation in Human Colon Cancer Cells.

Caudal-type homeobox transcription factor 2 (CDX2) is a master regulator of intestinal development and maintenance of the intestinal epithelium. We previously revealed that CDX2Low colorectal cancers (CRCs) were associated with poor survival and differential response to adjuvant chemotherapy. MicroRNAs (miRNAs), a class of non-coding RNAs typically composed of fewer than 25 nucleotides, are known to regulate gene expression and signaling pathways. This study aimed to identify oncogenic miRNAs induced by CDX2 in CRC. HCT116 cells were cultured and transfected with CDX2 siRNA. The expression levels of four oncogenic miRNAs (miR-9, miR-25, miR-106b and miR-221) were quantified by RT-qPCR. To understand whether CDX2 represented a key regulator of miR-221 expression in vivo, we analyzed the relationship between CDX2 and miR-221expression levels in the TCGA COAD database (n=454). The expression level of miR-221 was significantly up-regulated in CDX2 knockdown cells (n=2, p<0.05). In the TCGA database, we observed an inverse correlation between CDX2 and miR-221 expression levels, consistent with our in vitro data (r=-0.114, p=0.0149). Furthermore, the expression level of miR-221 was significantly elevated in patients with CDX2Low CRC (p<0.05). Knockdown of CDX2 induces microRNA-221 up-regulation in human CRC. Further research is warranted to elucidate the molecular mechanisms underlying miR-221 up-regulation in CDX2Low CRCs.

NKX2.5 coding exons sequencing reveals novel non-synonymous mutations in patients with sporadic congenital heart diseases among the Tanzanian population

BackgroundThe evolutionally conserved homeobox transcription factor NKX2-5 has been at the forefront in the field of cardiac biology, providing molecular insights into the mechanisms of cardiac development and disease. This homodomain transcription factor is a central regulator of cardiac development and is expressed in both the first and second heart fields (FHF and SHF). Mutations in the NKX2-5 gene have been linked to sporadic cases of congenital heart disease (CHD), making it a significant target for research and study. While several studies have been conducted on Caucasian populations, there is a dearth of knowledge on the effects of NKX2-5 gene mutations in other settings, underscoring the need for further investigation. Due to differences in geographical and ancestral origin, we hypothesize that mutations may vary across different populations. Understanding the genetic factors that cause CHD is essential for providing effective genetic counseling and developing strategies for risk reduction. Additionally, identification of NKX2-5 mutations in individuals with CHDs is crucial because patients with CHDs are at a higher risk of progressive conduction disease and sudden cardiac death, and genetic information is taken into consideration while making decisions regarding pacemakers and implantable cardiac defibrillators. To determine the risk of congenital heart disease among infants, we conducted a study where we sequenced the exon 1 and exon 2 of NKX 2.5 in patients with sporadic CHDs, with the aim of identifying mutations in the NKX2.5 gene.ResultsIn this study, a novel frame-shift disease-causing mutation was discovered in patients with atrial-ventricular septal defect. The mutation, identified as c95_95 del A; cDNA.369–369 delA; g 369–369 delA, resulted in the substitution of phenylalanine to leucine (F295L), which in turn caused a truncated NKX2.5 protein. In addition, a non-synonymous mutation, g 316C > T; cDNA 316C > T leucine to arginine (L37R) substitution, was found in a patient with the tetralogy of Fallot, affecting protein function. Furthermore, a novel non-synonymous mutation identified as g 2295–2298; cDNA 755–758 delins AGGG, was predicted by mutation taster to be disease-causing in a ventricular septal defect. It is worth noting that none of these mutations were found among the control subjects, highlighting their potential significance in the pathogenesis of these cardiac defects.ConclusionMutations in the NKX2.5 gene are associated with congenital heart diseases and provide molecular insight into the pathogenesis of congenital heart diseases. We recommend that patients with NKX2.5 mutations have periodic screening for cardiac conduction abnormalities and be evaluated for potential implanted cardiac defibrillators and pacemakers.

The single RRM domain-containing protein SARP1 is required for establishment of the separation zone in Arabidopsis.

Abscission is the shedding of plant organs in response to developmental and environmental cues. Abscission involves cell separation between two neighboring cell types, residuum cells (RECs) and secession cells (SECs) in the floral abscission zone (AZ) in Arabidopsis thaliana. However, the regulatory mechanisms behind the spatial determination that governs cell separation are largely unknown. The class I KNOTTED-like homeobox (KNOX) transcription factor BREVIPEDICELLUS (BP) negatively regulates AZ cell size and number in Arabidopsis. To identify new players participating in abscission, we performed a genetic screen by activation tagging a weak complementation line of bp-3. We identified the mutant ebp1 (enhancer of BP1) displaying delayed floral organ abscission. The ebp1 mutant showed a concaved surface in SECs and abnormally stacked cells on the top of RECs, in contrast to the precisely separated surface in the wild-type. Molecular and histological analyses revealed that the transcriptional programming during cell differentiation in the AZ is compromised in ebp1. The SECs of ebp1 have acquired REC-like properties, including cuticle formation and superoxide production. We show that SEPARATION AFFECTING RNA-BINDING PROTEIN1 (SARP1) is upregulated in ebp1 and plays a role in the establishment of the cell separation layer during floral organ abscission in Arabidopsis.

Maternal genetics and diet modulate vitamin A homeostasis of the offspring and affect the susceptibility to obesity in adulthood in mice.

Perinatal nutrition exerts a profound influence on adult metabolic health. This study aimed to investigate whether increased maternal vitamin A (VA) supply can lead to beneficial metabolic phenotypes in the offspring. The researchers utilized mice deficient in the intestine-specific homeobox (ISX) transcription factor, which exhibit increased intestinal VA retinoid production from dietary β-carotene (BC). ISX-deficient dams were fed a VA-sufficient or a BC-enriched diet during the last week of gestation and the whole lactation period. Total retinol levels in milk and weanling livers were 2 to 2.5-fold higher in the offspring of BC-fed dams (BC offspring), indicating increased VA supplies during late gestation and lactation. The corresponding VAS and BC offspring (males and females) were compared at weaning and adulthood after being fed either a standard or high-fat diet (HFD) with regular VA content for 13 weeks from weaning. HFD-induced increases in adiposity metrics, such as fat depot mass and adipocyte diameter, were more pronounced in males than females and were attenuated or suppressed in the BC offspring. Notably, the BC offspring were protected from HFD-induced increases in circulating triacylglycerol levels and hepatic steatosis. These protective effects were associated with reduced food efficiency, enhanced capacity for thermogenesis and mitochondrial oxidative metabolism in adipose tissues, and increased adipocyte hyperplasia rather than hypertrophy in the BC offspring. In conclusion, maternal VA nutrition influenced by genetics may confer metabolic benefits to the offspring, with mild increases in late gestation and lactation protecting against obesity and metabolic dysregulation in adulthood.

Unveiling stem-like traits and chemoresistance mechanisms in ovarian cancer cells through the TGFβ1-PITX2A/B signaling axis.

Ovarian cancer (OC) is the deadliest gynecological malignancy, having a high mortality rate due to its asymptomatic nature, chemoresistance and recurrence. However, the proper mechanistic knowledge behind these phenomena is still inadequate. Cancer recurrence is commonly observed due to cancer stem cells which also show chemoresistance. We aimed to decipher the molecular mechanism behind chemoresistance and stemness in OC. Earlier studies suggested that PITX2, a homeobox transcription factor and its different isoforms are associated with OC progression upon regulating different signaling pathways. Moreover, they regulate the expression of drug efflux transporters in kidney and colon cancer, rendering chemoresistance properties in the tumor cell. Considering these backgrounds, we decided to look for the role of PITX2 isoforms in promoting stemness and chemoresistance in OC cells. In this study, PITX2A/B has been shown to promote stemness and to enhance the transcription of ABCB1. PITX2 has been discovered to augment ABCB1 gene expression by directly binding to its promoter. To further investigate the regulatory mechanism of PITX2 gene expression, we found that TGFβ signaling could augment the PITX2A/B expression through both SMAD and non-SMAD signaling pathways. Collectively, we conclude that TGFβ1-activated PITX2A/B induces stem-like features and chemoresistance properties in the OC cells.

Cerebellar output neurons impair non-motor behaviors by altering development of extracerebellar connectivity.

The capacity of the brain to compensate for insults during development depends on the type of cell loss, whereas the consequences of genetic mutations in the same neurons are difficult to predict. We reveal powerful compensation from outside the cerebellum when the excitatory cerebellar output neurons are ablated embryonically and demonstrate that the minimum requirement for these neurons is for motor coordination and not learning and social behaviors. In contrast, loss of the homeobox transcription factors Engrailed1/2 (EN1/2) in the cerebellar excitatory lineage leads to additional deficits in adult learning and spatial working memory, despite half of the excitatory output neurons being intact. Diffusion MRI indicates increased thalamo-cortico-striatal connectivity in En1/2 mutants, showing that the remaining excitatory neurons lacking En1/2 exert adverse effects on extracerebellar circuits regulating motor learning and select non-motor behaviors. Thus, an absence of cerebellar output neurons is less disruptive than having cerebellar genetic mutations.

A spatially resolved multiomic single-cell atlas of soybean development.

Cis -regulatory elements (CREs) precisely control spatiotemporal gene expression in cells. Using a spatially resolved single-cell atlas of gene expression with chromatin accessibility across ten soybean tissues, we identified 103 distinct cell types and 303,199 accessible chromatin regions (ACRs). Nearly 40% of the ACRs showed cell-type-specific patterns and were enriched for transcription factor (TF) motifs defining diverse cell identities. We identified de novo enriched TF motifs and explored conservation of gene regulatory networks underpinning legume symbiotic nitrogen fixation. With comprehensive developmental trajectories for endosperm and embryo, we uncovered the functional transition of the three sub-cell types of endosperm, identified 13 sucrose transporters sharing the DOF11 motif that were co-up-regulated in late peripheral endosperm and identified key embryo cell-type specification regulators during embryogenesis, including a homeobox TF that promotes cotyledon parenchyma identity. This resource provides a valuable foundation for analyzing gene regulatory programs in soybean cell types across tissues and life stages.

Evolutionary analysis of genes from WOX family and their expression profile in grape (Vitis vinifera) under different stresses.

The WUSCHEL-related homeobox (WOX) transcription factor family plays critical roles in plant growth, development, and stress adaptation, but the biological functions in response to various stress of the WOX gene family have not been extensively researched in grapevine (Vitis vinifera ). In this study, 12 grapevine WOXs were identified from the grapevine genome. Quantitative PCR and microarray expression profiling found that the expression of WOXs had an obvious tissue-specific pattern. Conjoint analysis between various tissues and treated materials indicated VvWUS1 expression is associated with expression of genes from grapevine rupestris stem pitting-associated virus; and VvWOX3 with grapevine fanleaf virus. The gene expression patterns of the WOXs in grape were different under salt stress, with VvWOX8/9 , VvWUS1 , and VvWOX3 responding more strongly to salt stress than control by 18.20-, 9.50-, and 9.19-fold. This study further improves understanding of the evolution and function of the WOX gene family, and offers a theoretical framework and reference for breeding grapevine to better tolerate adversity and permit cultivation of seedlings free of viruses.

CNSC-03. LINKING CELL FATE DETERMINATION IN THE EMBRYONIC FOREBRAIN TO PEDIATRIC HIGH-GRADE GLIOMA

Abstract BACKGROUND Pediatric high-grade gliomas are treatment resistant, usually fatal cancers encompassing diffuse midline glioma, K27-altered (DMG), and diffuse hemispheric glioma, G34R/V (DHG). Most patients harbour canonical and non-canonical mutations in histone variants H3.1 and H3.3, leading to global epigenetic dysregulation and stalled differentiation states as oligodendroglial progenitor cells (OPC) in DMG and GABAergic interneuron precursors in DHG. DLX2 is a homeobox transcription factor that directly represses OPC cell fate and promotes GABAergic interneuron cell fate and migration during early neurogenesis. Methods &amp; Results Our lab has shown DLX2 promoter occupancy of Gad1/Gad2, and early (Olig2, Nkx2.2) and late (Myt1, Plp1) genes required for OPC differentiation in vivo. Co-expression of DLX2 with these target sequences reduces reporter gene expression in vitro, and the Dlx1/Dlx2 double knockout (DKO) mouse showed increases in Olig2, Nkx2.2, and Plp-1 expression in vivo. Transient over-expression of a Dlx2-GFP construct into murine DMG cells resulted in significant increased expression of Gad1/2 isoforms and decreased Olig2 and Nkx2.2, global restoration of H3K27me3 and loss of H3K27 acetylation, as well as a reduction in migration, invasion, and colony formation in vitro. To validate in human pHGG, we first probed an RNA-seq database containing 62 patient-derived pHGG cell lines which demonstrated an inverse correlation between DLX2 expression and OLIG1/2. Cell fate changes in DHG cell lines were evaluated by knockout of DLX2 using CRISPR/Cas9. Concurrently, OLIG1/2-expressing DMG cell lines underwent stable transfection of a DLX2-mCherry overexpression construct in conjunction with a SOX2-BFP overexpression construct, confirmed by qPCR and immunoblot. Analysis of histone H3 marks, K27M, and OPC signature genes will be compared to OPC genes from Dlx1/Dlx2 DKO mouse ganglionic eminences. CONCLUSIONS Manipulation of DLX2 in pHGG provides a model system for assessing the contribution of a homeobox factor to cell fate decisions regulating differentiation and tumorigenicity.

The WUSCHEL-related homeobox transcription factor CsWOX3 negatively regulates fruit spine morphogenesis in cucumber (Cucumis sativus L.).

Cucumber (Cucumis sativus L.) is a widely cultivated crop with rich germplasm resources, holding significant nutritional value. It also serves as an important model for studying epidermal cell fate and sex determination. Cucumbers are covered with multicellular and unbranched trichomes, including a specific type called spines found on the surface of the fruit. The presence and density of these fruit spines determine the visual quality of cucumber fruits. However, the key regulatory genes and mechanisms underlying cucumber fruit spine development remain poorly understood. In this study, we identified a WUSCHEL-related homeobox (WOX) family gene CsWOX3, which functioned as a typical transcriptional repressor and played a negative role in fruit spine development. Spatial-temporal expression analysis revealed that CsWOX3 exhibited a relatively high expression level in the cucumber female floral organs, particularly in the fruit exocarp. Knockout of CsWOX3 using CRISPR/Cas9 resulted in a significant 2-to-3-fold increase in the diameter of fruit spines base, while overexpression led to a 17% decrease in the diameter compared to the wild-type. A SQUAMOSA PROMOTER BINDING PROTEIN-LIKE transcription factor CsSPL15 could directly bind and activate the expression of CsWOX3, thereby suppressing the expression of downstream auxin-related genes, such as CsARF18. Additionally, the RING-finger type E3 ubiquitin ligase CsMIEL1-like interacted with the HD domain of CsWOX3, which might result in the ubiquitination and subsequent alteration in protein stability of CsWOX3. Collectively, our study uncovered a WOX transcription factor CsWOX3 and elucidated its expression pattern and biological function. This discovery enhances our comprehension of the molecular mechanism governing cucumber fruit spine morphogenesis.

LEUTX regulates porcine embryonic genome activation in somatic cell nuclear transfer embryos

Emerging evidence highlights the regulatory role of paired-like (PRD-like) homeobox transcription factors (TFs) in embryonic genome activation (EGA). However, the majority of PRD-like genes are lost in rodents, thus prompting an investigation into PRD-like TFs in other mammals. Here, we showed that PRD-like TFs were transiently expressed during EGA in human, monkey, and porcine fertilized embryos, yet they exhibited inadequate expression in their cloned embryos. This study, using pig as the research model, identified LEUTX as a key PRD-like activator of porcine EGA through genomic profiling and found that LEUTX overexpression restored EGA failure and improved preimplantation development and cloning efficiency in porcine cloned embryos. Mechanistically, LEUTX opened EGA-related genomic regions and established histone acetylation via recruiting acetyltransferases p300 and KAT2A. These findings reveal the regulatory mechanism of LEUTX to govern EGA in pigs, which may provide valuable insights into the study of early embryo development for other non-rodent mammals.

Phytochrome B interacts with LIGULELESS1 to control plant architecture and density tolerance in maize

Over the past few decades, significant improvements in maize yield have been largely attributed to increased plant density of upright hybrid varieties rather than increased yield per plant. However, dense planting triggers shade avoidance responses (SARs) that optimize light absorption but impair plant vigor and performance, limiting yield improvement through increasing plant density. In this study, we demonstrated that high-density-induced leaf angle narrowing and stem/stalk elongation are largely dependent on phytochrome B (phyB1/B2), the primary photoreceptor responsible for perceiving red (R) and far-red (FR) light in maize. We found that maize phyB physically interacts with the LIGULELESS1 (LG1), a classical key regulator of leaf angle, to coordinately regulate plant architecture and density tolerance. The abundance of LG1 is significantly increased by phyB under high R:FR light (low density) but rapidly decreases under low R:FR light (high density), correlating with variations in leaf angle and plant height under various densities. In addition, we identified the homeobox transcription factor HB53 as a target co-repressed by both phyB and LG1 but rapidly induced by canopy shade. Genetic and cellular analyses showed that HB53 regulates plant architecture by controlling the elongation and division of ligular adaxial and abaxial cells. Taken together, these findings uncover the phyB-LG1-HB53 regulatory module as a key molecular mechanism governing plant architecture and density tolerance, providing potential genetic targets for breeding maize hybrid varieties suitable for high-density planting.

DLX genes and proteins in mammalian forebrain development.

The vertebrate Dlx gene family encode homeobox transcription factors that are related to the Drosophila Distal-less (Dll) gene and are crucial for development. Over the last ∼35 years detailed information has accrued about the redundant and unique expression and function of the six mammalian Dlx family genes. DLX proteins interact with general transcriptional regulators, and co-bind with other transcription factors to enhancer elements with highly specific activity in the developing forebrain. Integration of the genetic and biochemical data has yielded a foundation for a gene regulatory network governing the differentiation of forebrain GABAergic neurons. In this Primer, we describe the discovery of vertebrate Dlx genes and their crucial roles in embryonic development. We largely focus on the role of Dlx family genes in mammalian forebrain development revealed through studies in mice. Finally, we highlight questions that remain unanswered regarding vertebrate Dlx genes despite over 30 years of research.

Genome-Wide Identification and Characterization of Homeobox Transcription Factors in Phoma sorghina var. saccharum Causing Sugarcane Twisted Leaf Disease.

A homeobox transcription factor is a conserved transcription factor, ubiquitous in eukaryotes, that regulates the tissue formation of structure, cell differentiation, proliferation, and cancer. This study identified the homeobox transcription factor family and its distribution in Phoma sorghina var. saccharum at the whole genome level. It elucidated the gene structures and evolutionary characteristics of this family. Additionally, knockout experiments were carried out and the preliminary function of these transcription factors was studied. Through bioinformatics approaches, nine homeobox transcription factors (PsHOX1-PsHOX9) were identified in P. sorghina var. saccharum, and these contained HOX-conserved domains and helix-turn-helix secondary structures. Nine homeobox gene deletion mutants were obtained using the homologous recombinant gene knockout technique. Protoplast transformation was mediated by polyethylene glycol (PEG) and the transformants were identified using PCR. The knockouts of PsHOX1, PsHOX2, PsHOX3, PsHOX4, PsHOX6, PsHOX8, and PsHOX9 genes resulted in a smaller growth diameter in P. sorghina var. saccharum. In contrast, the knockouts of the PsHOX3, PsHOX6, and PsHOX9 genes inhibited the formation of conidia and led to a significant decrease in the pathogenicity. This study's results will provide insights for understanding the growth and development of P. sorghina var. saccharum. The pathogenic mechanism of the affected sugarcane will provide an essential theoretical basis for preventing and controlling sugarcane twisted leaf disease.

The Evolution of the WUSCHEL-Related Homeobox Gene Family in Dendrobium Species and Its Role in Sex Organ Development in D. chrysotoxum.

The WUSCHEL-related homeobox (WOX) transcription factor plays a vital role in stem cell maintenance and organ morphogenesis, which are essential processes for plant growth and development. Dendrobium chrysotoxum, D. huoshanense, and D. nobile are valued for their ornamental and medicinal properties. However, the specific functions of the WOX gene family in Dendrobium species are not well understood. In our study, a total of 30 WOX genes were present in the genomes of the three Dendrobium species (nine DchWOXs, 11 DhuWOXs, and ten DnoWOXs). These 30 WOXs were clustered into ancient clades, intermediate clades, and WUS/modern clades. All 30 WOXs contained a conserved homeodomain, and the conserved motifs and gene structures were similar among WOXs belonging to the same branch. D. chrysotoxum and D. huoshanense had one pair of fragment duplication genes and one pair of tandem duplication genes, respectively; D. nobile had two pairs of fragment duplication genes. The cis-acting regulatory elements (CREs) in the WOX promoter region were mainly enriched in the light response, stress response, and plant growth and development regulation. The expression pattern and RT-qPCR analysis revealed that the WOXs were involved in regulating the floral organ development of D. chrysotoxum. Among them, the high expression of DchWOX3 suggests that it might be involved in controlling lip development, whereas DchWOX5 might be involved in controlling ovary development. In conclusion, this work lays the groundwork for an in-depth investigation into the functions of WOX genes and their regulatory role in Dendrobium species' floral organ development.

Genome-wide analysis of the poplar homeobox gene family and the identification of PtHB180 as an important regulator of plant developmental processes and drought stress response

Homeobox (HB) transcription factors have been reported to regulate various developmental processes and hormone signaling and mediate plant adaption to abiotic stresses, including drought. As a major subfamily of HB family, KNOX genes have been widely studied in herbaceous plants. However, the behaviors of KNOX genes in regulating plant developmental processes and stress resistance in woody plants remain poorly understood. Here, we found a KNOX family gene in the model tree species Populus trichocarpa (hereafter “poplar”), PtHB180, which enhances drought tolerance by regulating developmental processes through auxin and gibberellin pathways and mediating the ABA signaling pathway leading to rapid stomatal closure. Overexpression lines of PtHB180 (PtHB180-OE) displayed pleiotropic phenotypes, including increased plant height and decreased leaf area by affecting auxin and/or gibberellin contents and signaling. PtHB180-OE plants also displayed improved drought tolerance under short- and long-term drought stress. Results of transcriptome sequencing suggested the involvement of genes related to ABA signaling in regulating drought tolerance in PtHB180-OE. Specifically, PtHB180-OE plants showed significantly enhanced stomatal sensitivity to exogenous ABA. Taken together, our results indicate that PtHB180 enhances drought tolerance in poplar via regulating plant architecture and mediating ABA signaling to close stomata. Therefore, PtHB180 can be used as a potential candidate gene to improve drought tolerance by genetic transformation in poplar and related plant species.

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.

Homeobox regulator Wilms Tumour 1 is displaced by androgen receptor at cis-regulatory elements in the endometrium of PCOS patients.

Decidualisation, the process whereby endometrial stromal cells undergo morphological and functional transformation in preparation for trophoblast invasion, is often disrupted in women with polycystic ovary syndrome (PCOS) resulting in complications with pregnancy and/or infertility. The transcription factor Wilms tumour suppressor 1 (WT1) is a key regulator of the decidualization process, which is reduced in patients with PCOS, a complex condition characterized by increased expression of androgen receptor in endometrial cells and high presence of circulating androgens. Using genome-wide chromatin immunoprecipitation approaches on primary human endometrial stromal cells, we identify key genes regulated by WT1 during decidualization, including homeobox transcription factors which are important for regulating cell differentiation. Furthermore, we found that AR in PCOS patients binds to the same DNA regions as WT1 in samples from healthy endometrium, suggesting dysregulation of genes important to decidualisation pathways in PCOS endometrium due to competitive binding between WT1 and AR. Integrating RNA-seq and H3K4me3 and H3K27ac ChIP-seq metadata with our WT1/AR data, we identified a number of key genes involved in immune response and angiogenesis pathways that are dysregulated in PCOS patients. This is likely due to epigenetic alterations at distal enhancer regions allowing AR to recruit cofactors such as MAGEA11, and demonstrates the consequences of AR disruption of WT1 in PCOS endometrium.

Transcriptional control of visual neural circuit development by GS homeobox 1.

As essential components of gene expression networks, transcription factors regulate neural circuit assembly. The homeobox transcription factor encoding gene, gs homeobox 1 (gsx1), is expressed in the developing visual system; however, no studies have examined its role in visual system formation. In zebrafish, retinal ganglion cell (RGC) axons that transmit visual information to the brain terminate in ten arborization fields (AFs) in the optic tectum (TeO), pretectum (Pr), and thalamus. Pretectal AFs (AF1-AF9) mediate distinct visual behaviors, yet we understand less about their development compared to AF10 in the TeO. Using gsx1 zebrafish mutants, immunohistochemistry, and transgenic lines, we observed that gsx1 is required for vesicular glutamate transporter, Tg(slc17a6b:DsRed), expression in the Pr, but not overall neuron number. gsx1 mutants have normal eye morphology, yet they exhibit impaired visual ability during prey capture. RGC axon volume in the gsx1 mutant Pr and TeO is reduced, and AF7 that is active during feeding is missing which is consistent with reduced hunting performance. Timed laser ablation of Tg(slc17a6b:DsRed)-positive cells reveals that they are necessary for AF7 formation. This work is the first to implicate gsx1 in establishing cell identity and functional neural circuits in the visual system.