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Adenoid cystic carcinoma (ACC) and basal cell adenoma (BCA) share many histological characteristics and often need a differential diagnosis in clinical pathology. Recently, we found homeobox protein engrailed‐1 (EN1) was a potential diagnostic marker for ACC in an organoids library of salivary gland tumors (SGTs). Here we aim to confirm EN1 as a differential diagnostic marker for ACC, and further investigate the regulatory mechanism and biological function of EN1 in tumor progression. The transcriptional analysis, quantitative polymerase chain reaction, Western blot and immunohistochemistry staining were performed and revealed that EN1 was specifically and highly expressed in ACC, and accurately differentiated ACC from BCA. Furthermore, TGFβ signaling pathway was found associated with ACC, and the regulation of EN1 through TGFβ was detected in the human ACC cell lines and patient‐derived organoids (PDOs). TGFβ‐induced EN1 was important in promoting tumor budding in the PDOs model. Interestingly, a high level of EN1 and TGFβ1 in the budding tips was observed in ACC clinical samples, and the expression of EN1 and TGFβ1 in ACC was significantly associated with the clinical stage. In summary, our study verified EN1 is a good diagnostic marker to differentiate ACC from BCA. TGFβ‐induced EN1 facilitates the tumor budding of ACC, which might be an important mechanism related to the malignant phenotype of ACC. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro. Methods: We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and diabetic-Ad-MSCs (DM-Ad-MSCs) into IPCs was compared morphologically then through determining the gene expression of β-cell markers including neurogenin-3 (Ngn-3), homeobox protein (Nkx6.1), musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and insulin-1 (Ins-1) and eventually, through performing glucose-stimulated insulin secretion test (GSIS). Finally, the therapeutic potential of N-Ad-MSCs and DM-Ad-MSCs transplantation was compared in vivo in STZ-induced diabetic animals. Results: Our results showed no significant difference in the characteristics of N-Ad-MSCs and DM-Ad-MSCs. However, we demonstrated a significant difference in their abilities to differentiate into IPCs in vitro morphologically in addition to β-cell markers expression, and functional assessment via GSIS test. Furthermore, the abilities of both Ad-MSCs to control hyperglycemia in diabetic rats in vivo was assessed through measuring fasting blood glucose (FBGs), body weight (BW), histopathological examination of both pancreas and liver and immunoexpression of insulin in pancreata of study groups. Conclusion: Our findings reveal the effectiveness of N-Ad-MSCs in differentiating into IPCs in vitro and controlling the hyperglycemia of STZ-induced diabetic rats in vivo compared to DM-Ad-MSCs. [ABSTRACT FROM AUTHOR]

Gene function verification is a crucial step in studying the molecular mechanisms regulating various plant life activities. However, a stable and efficient homologous genetic transgenic system for herbaceous peonies has not been established. In this study, using virus-induced gene silencing technology (VIGS), a highly efficient homologous transient verification system with distinctive advantages was proposed, which not only achieves true "intact-plant" infiltration but also minimizes the operation. One-year-old roots of the representative species, Paeonia lactiflora Pall., were used as the materials; prechilling (4 °C) treatment for 3–5 weeks was applied as a critical precondition for P. lactiflora to acquire a certain chilling accumulation. A dormancy-related gene named HOMEOBOX PROTEIN 31 (PlHB31), believed to negatively regulate bud endodormancy release (BER), was chosen as the target gene in this study. GFP fluorescence was detected in directly infiltrated and newly developed roots and buds; the transgenic plantlets exhibited remarkably earlier budbreak, and PlHB31 was significantly downregulated in silenced plantlets. This study established a homologous transient silencing system featuring intact-plant infiltration and minimized manipulation for gene function research, and also offers technical support and serves as a theoretical basis for gene function discovery in numerous other geophytes. [ABSTRACT FROM AUTHOR]

KNOTTED-LIKE HOMEOBOX (KNOX) proteins are homeodomain containing transcription factors, and regulate many aspects of plant development through homo or heterodimerization with another group of TALE transcription factors known as BELL. In Medicago truncatula the MtKNOX3 gene is involved in nodule development. In this work, we hypothesized that MtKNOX3 involvement in the activation of cytokinin signaling during nodule development could be through heterodimerization with BELL proteins. Thereby, the expression of different BELL genes in Medicago was analyzed, and it was shown that the expression of Medtr8g078480 and Medtr8g098815 genes increases during nodule development. Besides, the Medtr8g078480 shows a co-expression pattern with MtKNOX3 at different developmental stages of nodule development. Afterward, the interaction of MtKNOX3 with the MtBELL1-2 (Medtr8g078480) protein was shown using docking, and their stability was analyzed by molecular dynamic simulation and mmpbsa methods. Moreover, the stability of MtKNOX3- Medtr8g078480 heterodimers was compared with the MtKNOX3 homodimer. [ABSTRACT FROM AUTHOR]

Activating transcription factor 5 (ATF5) is a transcription factor that belongs to the cAMP-response element-binding protein/ATF family and is essential for the differentiation and survival of sensory neurons in mouse olfactory organs. However, transcriptional target genes for ATF5 have yet to be identified. In the present study, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) experiments were performed to verify ATF5 target genes in the main olfactory epithelium and vomeronasal organ in the postnatal pups. ChIP-qPCR was conducted using hemagglutinin (HA)-tagged ATF5 knock-in olfactory organs. The results obtained demonstrated that ATF5-HA fusion proteins bound to the CCAAT/enhancer-binding protein-ATF response element (CARE) site in the enhancer region of nescient helix-loop-helix 1 (Nhlh1), a transcription factor expressed in differentiating olfactory and vomeronasal sensory neurons. Nhlh1 mRNA expression was downregulated in ATF5-deficient (ATF5−/−) olfactory organs. The LIM/homeobox protein transcription factor Lhx2 co-localized with ATF5 in the nuclei of olfactory and vomeronasal sensory neurons and bound to the homeodomain site proximal to the CARE site in the Nhlh1 gene. The CARE region of the Nhlh1 gene was enriched by the active enhancer marker, acetyl-histone H3 (Lys27). The present study identified Nhlh1 as a novel target gene for ATF5 in murine olfactory organs. ATF5 may upregulate Nhlh1 expression in concert with Lhx2, thereby promoting the differentiation of olfactory and vomeronasal sensory neurons. [ABSTRACT FROM AUTHOR]

Vision is mainly based on two different tasks, object detection and color discrimination, carried out by photoreceptor (PR) cells. The Drosophila compound eye consists of ~800 ommatidia. Every ommatidium contains eight PR cells, six outer cells (R1-R6) and two inner cells (R7 and R8), by which object detection and color vision are achieved, respectively. Expression of opsin genes in R7 and R8 is highly coordinated through the instructive signal from R7 to R8, and two major ommatidial subtypes are distributed stochastically; pale type expresses Rh3/Rh5 and yellow type expresses Rh4/Rh6 in R7/R8. The homeodomain protein Defective proventriculus (Dve) is expressed in yellow-type R7 and in six outer PRs, and it is involved in Rh3 repression to specify the yellow-type R7. dve mutant eyes exhibited atypical coupling, Rh3/Rh6 and Rh4/Rh5, indicating that Dve activity is required for proper opsin coupling. Surprisingly, Dve activity in R1 is required for the instructive signal, whereas activity in R6 and R7 blocks the signal. Our results indicate that functional coupling of two different neurons is established through signaling pathways from adjacent neurons that are functionally different. [ABSTRACT FROM AUTHOR]

Background: N6‐methyladenosine (m6A) modification interacting microRNAs (miRNAs) have been confirmed to participate in nasopharyngeal carcinoma (NPC) progression. This research investigated miR‐1908‐5p's function and regulatory mechanism in the tumorigenesis of NPC via m6A modification and targeting a key gene. Methods: The levels of miR‐1908‐5p, homeodomain‐only protein homeobox (HOPX), and methyltransferase‐like 3 (METTL3) expressions were detected via RT‐qPCR. The correlation between miR‐1908‐5p and the HOPX/METTL3 axis, as well as their regulatory mechanism, was investigated by dual luciferase reporter, western blotting, and MeRIP assays. Moreover, the bio‐functions of miR‐1908‐5p, HOPX, and METTL3 in NPC were explored through CCK8, transwell, caspase‐3 activity, and xenograft tumor assays. Results: RT‐qPCR results indicated a miR‐1908‐5p upregulation in NPC. Knocking down miR‐1908‐5p diminished the NPC cell viability and migration in vitro. In vivo, downregulating miR‐1908‐5p repressed NPC cell tumor growth. Moreover, HOPX was specifically targeted by miR‐1908‐5p, and HOPX downregulation led to reversal of the anti‐tumor impact of the miR‐1908‐5p inhibitor against NPC cell malignancy. Also, METTL3 could mediate the m6A modification of miR‐1908‐5p to regulate its influence on NPC cells. Conclusion: This study demonstrated that the METTL3‐mediated m6A modification of miR‐1908‐5p enhanced the tumorigenesis of NPC by targeting HOPX. These findings propose new insights for NPC diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is a common pathology in the advanced stage of cardiovascular diseases, which leads to cardiac systolic and diastolic dysfunction. It is important to prevent cardiac fibrosis during myocardial injury. The transcription factor Prrx1 is involved in cancer‐associated fibrosis and other organ fibrosis. However, the role and mechanism of Prrx1 in cardiac fibrosis deserves further exploration. We identified that overexpressed Prrx1 promoted the proliferation and migration of cardiac fibroblasts, and transform cardiac fibroblasts to myofibroblasts in vitro. We demonstrated that the expression of Prrx1 is upregulated in TGF‐β1‐treated fibroblasts. And silencing Prrx1 could attenuate cardiac fibrosis induced by TGF‐β1 in vitro. In addition, a Twist1‐paired‐related homeobox 1 (Prrx1)‐tenascin‐C (TNC) positive feedback loop (PFL) combined with Twist1, Prrx1, and TNC activated fibroblasts, which was the mechanism the Prrx1 in cardiac fibrosis. In conclusion, our findings showed that the deficiency of Prrx1 attenuated cardiac fibrosis in vitro and reveal a novel Twist1‐Prrx1‐TNC PFL in the regulation of cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Background: Homeodomain protein transforming growth factor beta-induced factor 2 like, X-linked (TGIF2 LX) has been demonstrated to act as a transcription factor and regulate cancer cell proliferation. Long non-coding RNAs (lncRNAs) are well known as molecular regulators of colorectal cancer (CRC). Our aim was to evaluate the clinical and biological significance of TGIF2 LX and its effect on lncRNAs regulator of reprogramming (ROR) and X-inactive specific transcript (XIST) expression in CRC cells. Materials and Methods: Thirty-six CRC tissues and 22 adjacent normal colorectal tissues were subjected to RNA extraction and analysis of TGIF2 LX gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). The human SW1116 cell line was transfected with cDNA for the TGIF2 LX gene. Microscopic analysis, reverse transcriptase PCR, and western blotting were used for confirming at transcriptional and translational levels. Methyl thiazolyl tetrazolium and colony formation assays were applied for evaluating the in vitro cell viability and colony-forming ability, respectively. LncRNA expression analysis was carried out using qRT-PCR. Results: The results showed that the expression levels of TGIF2 LX were significantly downregulated in CRC tissues compared to adjacent normal tissues (P = 0.032). Furthermore, the overexpression of TGIF2 LX could reduce the CRC cell line proliferation. The gene expression analysis revealed a significantly reduced level of lncRNA ROR and lncRNA XIST in TGIF2 LX-transfected SW1116 cells compared to nontransfected cells. Conclusion: Our findings provided evidence of molecular mechanisms by which TGIF2 LX may interact with lncRNAs ROR and XSIST to regulate CRC development by acting as a tumor suppressor. Thus, this protein may potentially be a promising option for CRC gene-based therapeutic strategies. [ABSTRACT FROM AUTHOR]

The INK4/ARF locus regulates senescence and is frequently altered in cancer. In normal cells, the INK4/ARF locus is found silenced by Polycomb repressive complexes (PRCs). Which are the mechanisms responsible for the recruitment of PRCs to INK4/ARF and their other target genes remains unclear. In a genetic screen for transcription factors regulating senescence, we identified the homeodomain-containing protein HLX1 (H2.0-like homeobox 1). Expression of HLX1 extends cellular lifespan and blunts oncogene-induced senescence. Using quantitative proteomics, we identified p16INK4a as the key target mediating the effects of HLX1 in senescence. HLX1 represses p16INK4a transcription by recruiting PRCs and HDAC1. This mechanism has broader implications, as HLX1 also regulates a subset of PRC targets besides p16INK4a. Finally, sampling members of the Homeobox family, we identified multiple genes with ability to repress p16INK4a. Among them, we found HOXA9 (Homeobox A9), a putative oncogene in leukaemia, which also recruits PRCs and HDAC1 to regulate p16INK4a. Our results reveal an unexpected and conserved interplay between homeodomain-containing proteins and PRCs with implications in senescence, development and cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] • GG improves depressive behavior in CUMS mice. • GG mainly improves neuronal apoptosis, theredy improving the behavior of depression. • HIPK2 SUMOylation modification is involved in neuronal apoptosis, and GG regulates depression-related neuronal apoptosis by promoting HIPK2 SUMOylation. Depression is a common mental illness with more than 280 million sufferers worldwide. Inflammation, particularly the c-Jun amino-terminal kinase (JNK) pathway, contributes to depression development and neuronal apoptosis. Gardenia is a herb with therapeutic effects on depression that has been shown to inhibit neuronal apoptosis. However, one of the components in gardenia, Genipin 1-O-β-D-gentiobioside(GG), has been less studied for its mechanism on depression. Thus, in the current study, we investigate how Genipin 1-O-β-D-gentiobioside improves depression and elucidate its possible mechanism of action. In this investigation, we utilize a chronic unpredictable mild stress (CUMS) mouse model and corticosterone-induced primary cortical neurons to examine the role of GG in ameliorating depressive symptoms and neuronal apoptosis. TUNEL staining and flow cytometry assessed the effects of GG on neuronal apoptosis. Western Blot analyses and immunofluorescence assays apoptosis-related proteins in the prefrontal cortex and primary neurons. The site of action of GG in regulating homeodomain interacting protein kinase 2 (HIPK2) SUMOylation was further explored in primary neurons. We constructed siRNA-SUMO1 vectors to transfect primary neuronal cells with intracellular SUMO1 knockdown. Proximity ligation assay (PLA) experiments were performed on primary neurons according to the instructions of the assay kit to observe the physical relationship between HIPK2 and SUMO1. We predicted the HIPK2 SUMOylation modification site by an online database and constructed vectors to target and site-directed mutagenesis, then to transfected primary neuronal cells. The results showed that GG effectively alleviated depressive-like behaviours, down-regulated apoptosis-related proteins (p-JNK, Bax, Cleaved-Caspase-3), and inhibited neuronal apoptosis in CUMS-induced depressed mice and corticosterone-induced primary cortical neurons. We reveal a complex mechanism underlying the link between GG, SUMOylation of HIPK2, and complex pathways of neuronal apoptosis regulation. K326 and K1189 are the key SUMOylation sites regulated by GG in intricate interactions of apoptosis-related proteins. Our study demonstrated that GG exerts antidepressant-like actions through neuroprotective effects by inhibiting the apoptosis of prefrontal cortex neurons, revealing the mechanism of GG inhibition of JNK phosphorylation by enhancing HIPK2 SUMOylation. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) represent a critical stromal component of metastatic niche and promote metastasis in patients with ovarian cancer (OC). Here, we try to further understand the mechanism by which CAFs-derived exosomes (CAFs-Exo) promoted angiogenesis in OC. We intersected differentially expressed genes in OC cells after CAFs-Exo treatment in the GSE147610 dataset with a list of transcription factors to identify homeobox protein hox-D11 (HOXD11) as a possible cargo of CAFs-Exo. HOXD11 encapsulated by CAFs-Exo enhanced colony formation, migration, and invasion of OC cells. HOXD11 bound to the promoter of fibronectin (FN1) and promoted its transcription. HOXD11 knockdown from CAFs-Exo significantly repressed the VEGF and CD31 protein expression and tube formation, viability, and migration of human umbilical vein endothelial cells (HUVEC) and slowed angiogenesis and tumor growth in mice. Furthermore, we found that overexpression of FN1 increased the expression of angiogenic factors and activity of HUVEC in the presence of HOXD11 knockdown. These results verify the significant contribution of CAFs-Exo to angiogenesis in OC, which could be partially due to the promotion of FN1 mediated by HOXD11. [ABSTRACT FROM AUTHOR]

Brassinosteroid (BR) phytohormones play crucial roles in regulating internode elongation in rice (Oryza sativa). However, the underlying mechanism remains largely unclear. The dwarf and low-tillering (dlt) mutant is a mild BR-signaling-defective mutant. Here, we identify two dlt enhancers that show more severe shortening of the lower internodes compared to the uppermost internode (IN1). Both mutants carry alleles of ORYZA SATIVA HOMEOBOX 15 (OSH15), the founding gene for dwarf6-type mutants, which have shortened lower internodes but not IN1. Consistent with the mutant phenotype, OSH15 expression is much stronger in lower internodes, particularly in IN2, than IN1. The osh15 single mutants have impaired BR sensitivity accompanied by enhanced BR synthesis in seedlings. DLT physically interacts with OSH15 to co-regulate many genes in seedlings and internodes. OSH15 targets and promotes the expression of the BR receptor gene BR INSENSITIVE1 (OsBRI1), and DLT facilitates this regulation in a dosage-dependent manner. In osh15, dlt, and osh15 dlt, BR levels are higher in seedlings and panicles, but unexpectedly lower in internodes compared with the wild-type. Taken together, our results suggest that DLT interacts with OSH15, which functions in the lower internodes, to modulate rice internode elongation via orchestrating BR signaling and metabolism. [ABSTRACT FROM AUTHOR]

Wilms tumour is a paediatric malignancy with features of halted kidney development. Here, we demonstrate that the Iroquois homeobox genes IRX3 and IRX5 are essential for mammalian nephrogenesis and govern the differentiation of Wilms tumour. Knock-out Irx3 - /Irx5 - mice showed a strongly reduced embryonic nephron formation. In human foetal kidney and Wilms tumour, IRX5 expression was already activated in early proliferative blastema, whereas IRX3 protein levels peaked at tubular differentiation. Accordingly, an orthotopic xenograft mouse model of Wilms tumour showed that IRX3 -/- cells formed bulky renal tumours dominated by immature mesenchyme and active canonical WNT/β-catenin-signalling. In contrast, IRX5 -/- cells displayed activation of Hippo and non-canonical WNT-signalling and generated small tumours with abundant tubulogenesis. Our findings suggest that promotion of IRX3 signalling or inhibition of IRX5 signalling could be a route towards differentiation therapy for Wilms tumour, in which WNT5A is a candidate molecule for enforced tubular maturation. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland., (© 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)

The reason why different types of vertebrate nerve cells are generated in a particular sequence is still poorly understood. In the vertebrate retina, homeobox genes play a crucial role in establishing different cell identities. Here we provide evidence of a cellular clock that sequentially activates distinct homeobox genes in embryonic retinal cells, linking the identity of a retinal cell to its time of generation. By in situ expression analysis, we found that the three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed but not translated in early retinal progenitors. Their translation requires cell cycle progression and is sequentially activated in photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). Furthermore, by in vivo lipofection of "sensors" in which green fluorescent protein translation is under control of the 3' untranslated region (UTR), we found that the 3' UTRs of Xotx5b, Xvsx1, and Xotx2 are sufficient to drive a spatiotemporal pattern of translation matching that of the corresponding proteins and consistent with the time of generation of photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). The block of cell cycle progression of single early retinal progenitors impairs their differentiation as photoreceptors and bipolar cells, but is rescued by the lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first evidence to our knowledge that vertebrate homeobox proteins can work as effectors of a cellular clock to establish distinct cell identities.

Drought stress has detrimental effects on crop productivity worldwide. A strong root system is crucial for maintaining water and nutrients uptake under drought stress. Wild watermelons possess resilient roots with excellent drought adaptability. However, the genetic factors controlling this trait remain uninvestigated. In this study, we conducted a bulk segregant analysis (BSA) on an F2 population consisting of two watermelon genotypes, wild and domesticated, which differ in their lateral root development under drought conditions. We identified two quantitative trait loci (qNLR_Dr. Chr01 and qNLR_Dr. Chr02) associated with the lateral root response to drought. Furthermore, we determined that a small region (0.93 Mb in qNLR_Dr. Chr01) is closely linked to drought adaptation through quantitative trait loci (QTL) validation and fine mapping. Transcriptome analysis of the parent roots under drought stress revealed unique effects on numerous genes in the sensitive genotype but not in the tolerant genotype. By integrating BSA, fine mapping, and the transcriptome, we identified six genes, namely L-Ascorbate Oxidase (AO), Cellulose Synthase-Interactive Protein 1 (CSI1), Late Embryogenesis Abundant Protein (LEA), Zinc-Finger Homeodomain Protein 2 (ZHD2), Pericycle Factor Type-A 5 (PFA5), and bZIP transcription factor 53-like (bZIP53-like), that might be involved in the drought adaptation. Our findings provide valuable QTLs and genes for marker-assisted selection in improving water-use efficiency and drought tolerance in watermelon. They also lay the groundwork for the genetic manipulation of drought-adapting genes in watermelon and other Cucurbitacea species. [ABSTRACT FROM AUTHOR]

Rice blast is one of the most destructive diseases of rice and is caused by the fungus Magnaporthe oryzae. The disease causes enormous yield losses in rice production worldwide. The rice blast fungus delivers effector proteins into rice cells. The effector proteins play an essential role in fungal virulence by manipulating and controlling host cellular pathways and inhibiting host immune responses to enhance pathogenicity. An effector gene, AvrPi9, which corresponds to the resistance gene Pi9, was cloned and characterized. However, a regulatory molecular mechanism for AvrPi9 gene expression has not been determined. In this study, the genetic variation of the AvrPi9 and its promoter function were characterized. The results showed that 98% (116/118) of the samples carried the AvrPi9 gene without any sequence variation, whilst two isolates, 10576 from Kalasin and NYK56003 from Nakhon Nayok, lacked the AvrPi9 gene. A homeobox domain‐containing protein (MoHOX6) was identified as a candidate transcription factor. The AvrPi9 gene expression was delayed in the MoHOX6 knockout mutant. Moreover, the AvrPi9 promoter was able to drive the expression of a luciferase gene in rice protoplasts. This study provides the first insight into the function and regulation of the AvrPi9 promoter of rice blast fungus. [ABSTRACT FROM AUTHOR]

The Jumonji-C (JmjC) family of lysine demethylases (KDMs) (JMJC-KDMs) plays an essential role in controlling gene expression and chromatin structure. In most cases, their function has been attributed to the demethylase activity. However, accumulating evidence demonstrates that these proteins play roles distinct from histone demethylation. This raises the possibility that they might share domains that contribute to their functional outcome. Here, we show that the JMJC-KDMs contain low-complexity domains and intrinsically disordered regions (IDR), which in some cases reached 70% of the protein. Our data revealed that plant homeodomain finger protein (PHF2), KDM2A, and KDM4B cluster by phase separation. Moreover, our molecular analysis implies that PHF2 IDR contributes to transcription regulation. These data suggest that clustering via phase separation is a common feature that JMJC-KDMs utilize to facilitate their functional responses. Our study uncovers a novel potential function for the JMJC-KDM family that sheds light on the mechanisms to achieve the competent concentration of molecules in time and space within the cell nucleus. [ABSTRACT FROM AUTHOR]

Mesenchyme homeobox protein 2 (MEOX2) is a transcription factor involved in mesoderm differentiation, including development of bones, muscles, vasculature and dermatomes. We have previously identified dysregulation of MEOX2 in fibroblasts from Congenital Insensitivity to Pain patients, and confirmed that btn, the Drosophila homologue of MEOX2, plays a role in nocifensive responses to noxious heat stimuli. To determine the importance of MEOX2 in the mammalian peripheral nervous system, we used a Meox2 heterozygous (Meox2+/−) mouse model to characterise its function in the sensory nervous system, and more specifically, in nociception. MEOX2 is expressed in the mouse dorsal root ganglia (DRG) and spinal cord, and localises in the nuclei of a subset of sensory neurons. Functional studies of the mouse model, including behavioural, cellular and electrophysiological analyses, showed altered nociception encompassing impaired action potential initiation upon depolarisation. Mechanistically, we noted decreased expression of Scn9a and Scn11a genes encoding Nav1.7 and Nav1.9 voltage‐gated sodium channels respectively, that are crucial in subthreshold amplification and action potential initiation in nociceptors. Further transcriptomic analyses of Meox2+/− DRG revealed downregulation of a specific subset of genes including those previously associated with pain perception, such as PENK and NPY. Based on these observations, we propose a novel role of MEOX2 in primary afferent nociceptor neurons for the maintenance of a transcriptional programme required for proper perception of acute and inflammatory noxious stimuli. [ABSTRACT FROM AUTHOR]

Sevoflurane (Sev) is a widely used inhalational anesthetic for general anesthesia in children. Previous studies have confirmed that multiple exposures to inhaled anesthetic can induce long-term neurotoxicity in newborn mice. However, the underlying mechanisms remain elusive. In this study, we investigated the role of homeodomain interacting protein kinase 2 (HIPK2), a stress activating kinase involved in neural survival and synaptic plasticity, and its underlying mechanism in sevoflurane-induced neurotoxicity. Empirical study showed that neuronal apoptosis was elevated after exposure to sevoflurane. Meanwhile, up-regulation of HIPK2 and AKT/mTOR signaling was observed in primary hippocampal neurons and hippocampus in mice upon anesthetic exposure. A64, antagonist of HIPK2, could significantly reduce increased apoptosis and activation of AKT/mTOR induced by sevoflurane. AKT antagonist MK2206 partially alleviated neuronal apoptosis without affecting the expression of HIPK2. Experimental results demonstrated a crucial role of HIPK2/AKT/mTOR signaling in neurotoxicity of sevoflurane. Thus, HIPK2/AKT/mTOR signaling can serve as a potential target for the protection of inhalation anesthesia-induced cytotoxicity in the future. [ABSTRACT FROM AUTHOR]

Summary: Angiogenic homeobox genes regulate the behaviour of endothelial cells (ECs) during angiogenesis, so the aim of this study was to determine whether expression of these genes may be a determinant of malignancy in canine haemangiosarcoma (HSA). Homeobox proteins were evaluated immunohistochemically in tissue samples from canine HSAs (n =78), haemangiomas (HAs; n =30) and samples of granulation tissue (n =8). Active ECs in granulation tissue were positively labelled by antisera specific for HoxA9, HoxB3, HoxD3, HoxB7, Pbx1 and Meis1. Quiescent ECs in granulation tissue did not express HoxD3 and Pbx1. There were significantly more neoplastic cells positively labelled for HoxA9, HoxB3, HoxD3 and Pbx1 in HSA compared with HA. Almost all tumours were positive for HoxB7 and Meis1. HoxB3, HoxD3, Pbx1 and Meis1 proteins were detected in 80–90% of the HSAs, but in <20% of the HAs. Overall, homeobox protein expression in HSA appears to have a phenotype similar to that of active ECs in angiogenesis. The expression of homeobox genes associated with angiogenesis might be associated with the malignant growth of HSA. [Copyright &y& Elsevier]

Chaperonin ProteinIn article number 2402816, Yan Hu, Tianzhen Zhang, and co‐workers report a chaperonin protein controls upward‐curling leaves margin. They explain this phenotype that had existed for nearly a century. Chaperonin protein GHCU, homeodomain protein KNGH1 and auxin play roles in it..By Yihao Zang; Chenyu Xu; Lishan Yu; Longen Ma; Lisha Xuan; Sunyi Yan; Yayao Zhang; Yiwen Cao; Xiaoran Li; Zhanfeng Si; Jieqiong Deng; Tianzhen Zhang and Yan HuReported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

APETALA3 (AP3) and PISTILLATA (PI) are B‐class MADS‐box floral homeotic genes of Arabidopsis and are involved in specifying the identity of petals and stamens. In the present work, IiAP3 and IiPI, the respective orthologous genes of AP3 and PI, were cloned from Isatis indigotica. By expressing in ap3‐6 and pi‐1 homozygous mutant and in wild‐type Arabidopsis under the control of AP3 promoter or CaMV 35S promoter, we demonstrated that IiAP3 and IiPI were functionally equivalent to AP3 and PI of Arabidopsis. Referring to previous reports and the research results in the present work, expression patterns of AP3 and PI homologs are not the same in different angiosperms possessing diverse floral structures. It suggests that the alterations in expression may contribute to the changing morphology of flowers. To further determine the relationship between IiAP3 and IiPI, the coding sequences of the different structural regions in these two proteins were swapped with each other, and the data collected from transgenic Arabidopsis plants of the chimeric constructs suggested that MADS domain was irreplaceable for the function of IiAP3, K domain of IiAP3 was involved in specifying the identity of stamens, K domain of IiPI was mainly related to the formation of petals, and C‐terminal region of IiPI was involved in characterization of stamens. In addition, a complete KC region of these two proteins was more effective in phenotypic complementation of the mutants. [ABSTRACT FROM AUTHOR]

Background & Objective: Gastric cancer (GC) persists to be a major health issue globally, and the need to investigate new molecular markers for improving the survival of patients continues. CDX2 is a homeobox caudal protein family member encoded by the CDX2 gene and is probably playing a role in intestinal epithelial differentiation and proliferation. This study aimed to assess the expression of this protein in gastric cancer cells in addition to its correlation with multiple clinicopathological parameters. Methods: This observational retrospective study was carried out on 80 gastric cancer cases in Erbil, Iraq. CDX2 protein immunoexpression in tumor cells, as well as its correlation with several clinicopathological criteria, were investigated. Results: CDX2 was detected in 38.75% of GC patients. We found a significant correlation between CDX2 expression and the age of patients (P=0.02). Even though the protein was more expressed in tumors with negative lymphovascular invasion and intestinal GC, there was no significant correlation between the expression of this protein and invasion. In addition, CDX2 expression was not significantly correlated with patient gender, tumor grade, nodal status, and tumor stage. Conclusion: CDX2 expression was observed to be downregulated in younger patients. It could be due to the higher frequency of diffuse GC, in which CDX2 is expressed less than the intestinal type, in younger individuals. [ABSTRACT FROM AUTHOR]

The methyl-lysine readers plant homeodomain finger protein 20 (PHF20) and its homolog PHF20-like protein 1 (PHF20L1) are known components of the nonspecific lethal (NSL) complex that regulates gene expression through its histone acetyltransferase activity. In the current model, both PHF homologs coexist in the same NSL complex, although this was not formally tested; nor have the functions of PHF20 and PHF20L1 regarding NSL complex integrity and transcriptional regulation been investigated. Here, we perform an in-depth biochemical and functional characterization of PHF20 and PHF20L1 in the context of the NSL complex. Using mass spectrometry, genome-wide chromatin analysis, and proteindomain mapping, we identify the existence of two distinct NSL complexes that exclusively contain either PHF20 or PHF20L1. We show that the C-terminal domains of PHF20 and PHF20L1 are essential for complex formation with NSL, and the Tudor 2 domains are required for chromatin binding. The genome-wide chromatin landscape of PHF20-PHF20L1 shows that these proteins bind mostly to the same genomic regions, at promoters of highly expressed/housekeeping genes. Yet, deletion of PHF20 and PHF20L1 does not abrogate gene expression or impact the recruitment of the NSL complex to those target gene promoters, suggesting the existence of an alternative mechanism that compensates for the transcription of genes whose sustained expression is important for critical cellular functions. This work shifts the current paradigm and lays the foundation for studies on the differential roles of PHF20 and PHF20L1 in regulating NSL complex activity in physiological and diseases states. [ABSTRACT FROM AUTHOR]

Clip‐domain serine proteases (CLIPs) play important roles in insect innate immunity and development. Our previous studies indicated that CLIP13, an epidermis‐specific gene, was involved in cuticle remodeling during molting and metamorphosis in the silkworm, Bombyx mori. However, the transcriptional regulatory mechanism and regulatory pathways of CLIP13 remained unclear. In the present study, we investigated CLIP13 expression and the regulation pathway controlled by 20‐hydroxyecdysone (20E) in the silkworm. At the transcriptional level, expression of CLIP13 exhibited pronounced spatial and temporal specificity in different regions of the epidermis; homeodomain transcription factors POU‐M2, antennapedia (Antp), and abdominal‐B (Abd‐B) showed similar expression change trends as CLIP13 in the head capsule, thorax, and abdomen, respectively. Furthermore, results of cell transfection assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation demonstrated that POU‐M2, Antp, and Abd‐B were involved in the transcriptional regulation of CLIP13 by directly binding to their cis‐response elements in CLIP13 promoter. RNA interference‐mediated silencing of POU‐M2, Antp, and Abd‐B led to a decrease of CLIP13 expression in the head capsule, the epidermis of the 1st to 3rd thoracic segments and the 7th to 10th abdominal segments, respectively. Consistent with CLIP13, 20E treatment significantly upregulated expression of POU‐M2, Antp, and Abd‐B in the silkworm epidermis. Taken together, these data suggest that 20E positively regulates transcription of CLIP13 via homeodomain proteins POU‐M2, Antp, and Abd‐B in different regions of the silkworm epidermis during metamorphosis, thus affecting the molting process. Our findings provide new insight into the functions of homeodomain transcription factors in insect molting. [ABSTRACT FROM AUTHOR]

The KNOTTED1‐LIKE HOMEOBOX PROTEIN1 (KD1) gene is highly expressed in flower and leaf abscission zones (AZs), and KD1 was reported to regulate tomato flower pedicel abscission via alteration of the auxin gradient and response in the flower AZ (FAZ). The present work was aimed to further examine how KD1 regulates signaling factors and regulatory genes involved in pedicel abscission, by using silenced KD1 lines and performing a large‐scale transcriptome profiling of the FAZ before and after flower removal, using a customized AZ‐specific microarray. The results highlighted a differential expression of regulatory genes in the FAZ of KD1‐silenced plants compared to the wild‐type. In the TAPG4::antisense KD1‐silenced plants, KD1 gene expression decreased before flower removal, resulting in altered expression of regulatory genes, such as epigenetic modifiers, transcription factors, posttranslational regulators, and antioxidative defense factors occurring at zero time and before affecting auxin levels in the FAZ detected at 4 h after flower removal. The expression of additional regulatory genes was altered in the FAZ of KD1‐silenced plants at 4–20 h after flower removal, thereby leading to an inhibited abscission phenotype, and downregulation of genes involved in abscission execution and defense processes. Our data suggest that KD1 is a master regulator of the abscission process, which promotes abscission of tomato flower pedicels. This suggestion is based on the inhibitory effect of KD1 silencing on flower pedicel abscission that operates via alteration of various regulatory pathways, which delay the competence acquisition of the FAZ cells to respond to ethylene signaling. [ABSTRACT FROM AUTHOR]

Summary: Indole‐3‐acetic acid (IAA) is a predominant form of active auxin in plants. In addition to de novo biosynthesis and release from its conjugate forms, IAA can be converted from its precursor indole‐3‐butyric acid (IBA).The IBA‐derived IAA may help drive root hair elongation in Arabidopsis thaliana seedlings, but how the IBA‐to‐IAA conversion is regulated and affects IAA function requires further investigation.In this study, HOMEOBOX PROTEIN 24 (HB24), a transcription factor in the zinc finger‐homeodomain family (ZF‐HD family) of proteins, was identified. With loss of HB24 function, defective growth occurred in root hairs. INDOLE‐3‐BUTYRIC ACID RESPONSE 1 (IBR1), which encodes an enzyme involved in the IBA‐to‐IAA conversion, was identified as a direct target of HB24 for the control of root hair elongation. The exogenous IAA or auxin analogue 1‐naphthalene acetic acid (NAA) both rescued the root hair growth phenotype of hb24 mutants, but IBA did not, suggesting a role for HB24 in the IBA‐to‐IAA conversion.Therefore, HB24 participates in root hair elongation by upregulating the expression of IBR1 and subsequently promoting the IBA‐to‐IAA conversion. Moreover, IAA also elevated the expression of HB24, suggesting a feedback loop is involved in IBA‐to‐IAA conversion‐mediated root hair elongation. [ABSTRACT FROM AUTHOR]

Background: In hexaploid wheat, quantitative trait loci (QTL) and meta-QTL (MQTL) analyses were conducted to identify genomic regions controlling resistance to cereal cyst nematode (CCN), Heterodera avenae. A mapping population comprising 149 RILs derived from the cross HUW 468 × C 306 was used for composite interval mapping (CIM) and inclusive composite interval mapping (ICIM). Results: Eight main effect QTLs on three chromosomes (1B, 2A and 3A) were identified using two repeat experiments. One of these QTLs was co-localized with a previously reported wheat gene Cre5 for resistance to CCN. Seven important digenic epistatic interactions (PVE = 5% or more) were also identified, each involving one main effect QTL and another novel E-QTL. Using QTLs earlier reported in literature, two meta-QTLs were also identified, which were also used for identification of 57 candidate genes (CGs). Out of these, 29 CGs have high expression in roots and encoded the following proteins having a role in resistance to plant parasitic nematodes (PPNs): (i) NB-ARC,P-loop containing NTP hydrolase, (ii) Protein Kinase, (iii) serine-threonine/tyrosine-PK, (iv) protein with leucine-rich repeat, (v) virus X resistance protein-like, (vi) zinc finger protein, (vii) RING/FYVE/PHD-type, (viii) glycosyl transferase, family 8 (GT8), (ix) rubisco protein with small subunit domain, (x) protein with SANT/Myb domain and (xi) a protein with a homeobox. Conclusion: Identification and selection of resistance loci with additive and epistatic effect along with two MQTL and associated CGs, identified in the present study may prove useful for understanding the molecular basis of resistance against H. avenae in wheat and for marker-assisted selection (MAS) for breeding CCN resistant wheat cultivars. [ABSTRACT FROM AUTHOR]

Translational control is critical for cell fate transitions during development, lineage specification, and tumorigenesis. Here, we show that the transcription factor double homeobox protein 4 (DUX4), and its previously characterized transcriptional program, broadly regulates translation to change the cellular proteome. DUX4 is a key regulator of zygotic genome activation in human embryos, whereas misexpression of DUX4 causes facioscapulohumeral muscular dystrophy (FSHD) and is associated with MHC-I suppression and immune evasion in cancer. We report that translation initiation and elongation factors are disrupted downstream of DUX4 expression in human myoblasts. Genome-wide translation profiling identified mRNAs susceptible to DUX4-induced translation inhibition, including those encoding antigen presentation factors and muscle lineage proteins, while DUX4-induced mRNAs were robustly translated. Endogenous expression of DUX4 in human FSHD myotubes and cancer cell lines also correlated with reduced protein synthesis and MHC-I presentation. Our findings reveal that DUX4 orchestrates translational reprogramming by suppressing the cellular proteome while maintaining translation of DUX4-induced mRNAs to promote an early developmental program. Cellular reprogramming requires multifaceted regulation of gene expression. This study shows that DUX4 modulates multiple translational regulators to broadly suppress protein synthesis while promoting expression of DUX4-induced genes, suggesting a natural role in cell state conversion during development and a pathological role when expressed in cancer or muscular dystrophy. [ABSTRACT FROM AUTHOR]

Transcription factors (TFs) play critical roles in specifying many aspects of neuronal cell fate including dendritic morphology. How TFs are accurately regulated during neuronal morphogenesis is not fully understood. Here, we show that LIM homeodomain protein MEC-3, the key TF for C. elegans PVD dendrite morphogenesis, is regulated by both alternative splicing and an E3 ubiquitin ligase. The mec-3 gene generates several transcripts by alternative splicing. We find that mbl-1, the orthologue of the muscular dystrophy disease gene muscleblind-like (MBNL), is required for PVD dendrite arbor formation. Our data suggest mbl-1 regulates the alternative splicing of mec-3 to produce its long isoform. Deleting the long isoform of mec-3(deExon2) causes reduction of dendrite complexity. Through a genetic modifier screen, we find that mutation in the E3 ubiquitin ligase EEL-1 suppresses mbl-1 phenotype. eel-1 mutants also suppress mec-3(deExon2) mutant but not the mec-3 null phenotype. Loss of EEL-1 alone leads to excessive dendrite branches. Together, these results indicate that MEC-3 is fine-tuned by alternative splicing and the ubiquitin system to produce the optimal level of dendrite branches. Author summary: Dendrite morphology is essential for the proper functioning of neurons. Abnormalities in dendrite structure are associated with different neurological disorders like autism, schizophrenia, and Rett's syndrome. Using forward genetic approaches, we identify two new factors, alternative splicing regulator MBL-1 and E3 ubiquitin ligase EEL-1, which participate in regulating PVD dendrite morphogenesis in C. elegans. MBL-1 regulates the alternative splicing of transcription factor MEC-3 to produce its long isoform. EEL-1 reduces the amount of MEC-3 protein to ensure its correct expression level. Our findings indicate that the combination of alternative splicing and ubiquitin ligase on the level of a transcription factor to regulate dendrite morphogenesis, which is unexpected and original. Both mbl-1 and eel-1 are genes associated with diseases, and the transcription factor MEC-3 may act as their target, which will provide insight into the mechanism of these diseases. [ABSTRACT FROM AUTHOR]

Leaf margin morphology is an important quality trait affecting the commodity and environmental adaptability of crops. Brassica rapa is an ideal research material for exploring the molecular mechanisms underlying leaf lobe development. Here, we identified BrrA02.LMI1 to be a promising gene underlying the QTL qBrrLLA02 controlling leaf lobe formation in B. rapa, which was detected in our previous study. Sequence comparison analysis showed that the promoter divergences were the most obvious variations of BrrA02.LMI1 between parental lines. The higher expression level and promoter activity of BrrA02.LMI1 in the lobe-leafed parent indicated that promoter variations of BrrA02.LMI1 were responsible for elevating expression and ultimately causing different allele effects. Histochemical GUS staining indicated that BrrA02.LMI1 is mainly expressed at the leaf margin, with the highest expression at the tip of each lobe. Subcellular localization results showed that BrrA02.LMI1 was in the nucleus. The ectopic expression of BrrA02.LMI1 in A. thaliana resulted in a deep leaf lobe in the wild-type plants, and lobed leaf formation was disturbed in BrrA02.LMI11-downregulated plants. Our findings revealed that BrrA02.LMI1 plays a vital role in regulating the formation of lobed leaves, providing a theoretical basis for the selection and breeding of leaf-shape-diverse varieties of B. rapa. [ABSTRACT FROM AUTHOR]

Summary: Although tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukaemia (CML), TKI resistance remains a major challenge. Here, we demonstrated that plant homeodomain finger protein 8 (PHF8), a histone demethylase was aberrantly enriched in CML samples compared to healthy controls. PHF8 inhibited CML cell differentiation and promoted CML cell proliferation. Furthermore, the proliferation‐inhibited function of PHF8‐knockdown have stronger effect on imatinib mesylate (IM)‐resistant CML cells. Mechanistically, we identified that PHF8 as a transcriptional modulator interacted with the promoter of the BCR::ABL1 fusion gene and alters the methylation levels of H3K9me1, H3K9me2 and H3K27me1, thereby promoting BCR::ABL1 transcription. Overall, our study suggests that targeting PHF8, which directly regulates BCR::ABL1 expression, is a useful therapeutic approach for CML. [ABSTRACT FROM AUTHOR]

MicroRNA-21 (miR-21) plays an anti-apoptotic role following ischemia–reperfusion (I/R) injury (IRI) in vivo; however, its underlying mechanism remains unclear. The present study explored the effects of miR-21 and homeodomain interacting protein kinase 3 (HIPK3) on cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) in vitro. To this end, the rat cardiomyocyte H9C2 cell line was exposed to H/R and the roles of miR-21 and HIPK3 in regulating cell viability and apoptosis were evaluated by cell counting kit-8 assay, terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling, and flow cytometry. Immunofluorescence and Western blotting were performed to detect the expression/phosphorylation of apoptosis-related proteins. miR-21 expression was measured with quantitative real-time polymerase chain reaction. The putative interaction between miR-21 and HIPK3 was evaluated using the luciferase reporter assay. Our results showed that (i) miR-21 overexpression or HIPK3 down-regulation significantly attenuated H9C2 cells apoptosis after H/R, (ii) suppression of miR-21 expression promoted apoptosis, (iii) miR-21 overexpression inhibited HIPK3 expression, (iv) HIPK3 was the direct and main target of miR-21, (v) miR-21/HIPK3 formed part of a reciprocal, negative feedback loop, and (vi) HIPK3 down-regulation decreased FAS-mediated apoptosis by inhibiting the phosphorylation of FADD, which subsequently inhibited the expression of BAX and cleaved caspase-3 and increased the expression of BCL2. Our study indicates that miR-21 attenuates FAS-mediated cardiomyocyte apoptosis by regulating HIPK3 expression, which could eventually have important clinical implications for patients with acute myocardial infarction. [ABSTRACT FROM AUTHOR]

It compares proteins from krueppel C2H2-type zinc-finger protein family (upper sequences) with proteins from other families (bottom sequences) HT

Introduction: Transforming growth factor-beta-induced factor X-linked (TGIF2LX) as a homeodomain protein and TGF-β corepressor, could regulate proliferation of some cancer cells including colorectal cancer by some signaling pathways. Small non-coding RNAs (microRNA; miRNA) are known as molecular regulators of colorectal cancer that are involved in the processes of cell growth, proliferation, differentiation and apoptosis. The aim of this study was to evaluate the biological significance of TGIF2LX protein and its effect on the expression of oncogenic miRNAs miR-34a, miR-20a and miR-21 in colorectal cancer cells SW1116. Methods: Human SW1116 cell line and cell line transfected with cDNA encoding TGIF2LX gene were cultured in RPMI 1640 medium under appropriate conditions. MTT assay was used to assess cell viability in vitro. After RNA extraction from all cell groups and cDNA synthesis, miRNA expression analysis was performed using qReal-time PCR technique. Results: The results showed that the increased expression of TGIF2LX could reduce the proliferation of SW1116 cell line. Gene expression analysis showed that increased expression of TGIF2LX could significantly reduce the expression level of miR-21 (P<0.038). However, the expression levels of miR-34a and miR-20a in SW1116 cells transfected with TGIF2LX did not show a significant change compared to non-transfected cells (P>0.05). Conclusion: Our findings provide evidence of molecular mechanisms that the homeodomain protein TGIF2LX can act as a tumor suppressor in colorectal cancer cells by reducing miR-21 expression. Therefore, this protein can potentially be considered as a promising option for gene-based therapeutic strategies in this cancer. [ABSTRACT FROM AUTHOR]

The growth pattern of filamentous fungi can switch between hyphal radial polar growth and non-polar yeast-like cell growth depending on the environmental conditions. Asexual conidiation after radial polar growth is called normal conidiation (NC), while yeast-like cell growth is called microcycle conidiation (MC). Previous research found that the disruption of MaH1 in Metarhizium acridum led to a conidiation shift from NC to MC. However, the regulation mechanism is not clear. Here, we found MaMsn2, an Msn2 homologous gene in M. acridum, was greatly downregulated when MaH1 was disrupted (∆MaH1). Loss of MaMsn2 also caused a conidiation shift from NC to MC on a nutrient-rich medium. Yeast one-hybrid (Y1H) and electrophoretic mobility shift assay (EMSA) showed that MaH1 could bind to the promoter region of the MaMsn2 gene. Disrupting the interaction between MaH1 and the promoter region of MaMsn2 significantly downregulated the transcription level of MaMsn2, and the overexpression of MaMsn2 in ∆MaH1 could restore NC from MC of ∆MaH1. Our findings demonstrated that MaMsn2 played a role in maintaining the NC pattern directly under the control of MaH1, which revealed the molecular mechanisms that regulated the conidiation pattern shift in filamentous fungi for the first time. [ABSTRACT FROM AUTHOR]

First identified as a developmental gene, HOXB9 is also known to be involved in tumor biological processes, and its aberrant expression correlates with poor prognosis of various cancers. In this study, we isolated a homeodomain-less, novel HOXB9 variant (HOXB9v) from human breast cancer cell line-derived mRNA. We confirmed that the novel variant was produced from variationless HOXB9 genomic DNA. RT-PCR of mRNA isolated from clinical samples and reanalysis of publicly available RNA-seq data proved that the new transcript is frequently expressed in human breast cancer. Exogenous HOXB9v expression significantly enhanced the proliferation of breast cancer cells, and gene ontology analysis indicated that apoptotic signaling was suppressed in these cells. Considering that HOXB9v lacks key domains of homeobox proteins, its behavior could be completely different from that of the previously described variationless HOXB9. Because none of the previous studies on HOXB9 have considered the presence of HOXB9v, further research analyzing the two transcripts individually is warranted to re-evaluate the true role of HOXB9 in cancer. [ABSTRACT FROM AUTHOR]