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Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) has been identified as a crucial immune suppressor in human cancers, comparable to programmed cell death 1 ligand (PD-L1). However, the regulatory mechanisms underlying its transcriptional upregulation in human cancers remain largely unknown. Here, we show that the transcription factors ETS-1 and ETS-2 bound to the Siglec-15 promoter to enhance transcription and expression of Siglec-15 in hepatocellular carcinoma (HCC) cells and that transforming growth factor β-1 (TGF-β1) upregulated the expression of ETS-1 and ETS-2 and facilitated the binding of ETS-1 and ETS-2 to the Siglec-15 promoter. We further demonstrate that TGF-β1 activated the Ras/C-Raf/MEK/ERK1/2 signaling pathway, leading to phosphorylation of ETS-1 and ETS-2, which consequently upregulates the transcription and expression of Siglec-15. Our study defines a detailed molecular profile of how Siglec-15 is transcriptionally regulated which may offer significant opportunity for therapeutic intervention on HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) has been identified as a crucial immune suppressor in human cancers, comparable to programmed cell death 1 ligand (PD-L1). However, the regulatory mechanisms underlying its transcriptional upregulation in human cancers remain largely unknown. Here, we show that the transcription factors ETS-1 and ETS-2 bound to the Siglec-15 promoter to enhance transcription and expression of Siglec-15 in hepatocellular carcinoma (HCC) cells and that transforming growth factor β-1 (TGF-β1) upregulated the expression of ETS-1 and ETS-2 and facilitated the binding of ETS-1 and ETS-2 to the Siglec-15 promoter. We further demonstrate that TGF-β1 activated the Ras/C-Raf/MEK/ERK1/2 signaling pathway, leading to phosphorylation of ETS-1 and ETS-2, which consequently upregulates the transcription and expression of Siglec-15. Our study defines a detailed molecular profile of how Siglec-15 is transcriptionally regulated which may offer significant opportunity for therapeutic intervention on HCC immunotherapy.

HIV-1 is transcriptionally active in activated T helper (Th)-cells and inactive in naive or resting memory Th-cells. Ets-2 is a preinduction transcriptional repressor of the IL-2 gene in naive Th-cells and a candidate transcriptional repressor of HIV-1 in the same cells, because the −279 to −250 upstream region of HIV-1-LTR [repressor–activator target sequence (RATS)], that participates in HIV-1-LTR transcriptional silencing, encompasses the AAGGAG Ets-2 binding site. In this proof of concept study, we investigated whether Ets-2 represses the expression of HIV-1. To assess whether Ets-2 can repress HIV-1 transcriptional activation acting through RATS, we transfected Jurkat cells with an Ets-2 overexpression plasmid (pCDNA3-ets-2) or Ets-2 silencing plasmids (ets-2-shRNA) and, as target genes, plasmids carrying the whole HIV-1-LTR sequence (HIV-1-LTR-CAT) or two copies of the RATS sequence (2× RATS-CAT) or a point mutation in the Ets-2 binding site (2× mutantRATS-CAT) or CMV-CAT (control). Ets-2 overexpression resulted in a significant reduction of HIV-1-LTR-CAT and 2× RATS-CAT activities in stimulated cells, but not of the 2× mutantRATS-CAT or CMV-CAT. Ets-2 silencing led to increased activities of HIV-1-LTR-CAT and 2× RATS-CAT in unstimulated cells, but had no effect on the activities of 2× mutantRATS-CAT and CMV-CAT. To assess Ets-2 binding to HIV-1-LTR–RATS in naive Th-cells, we isolated naive Th-cell nuclear proteins and passed them through an Ets-2 antibody column; electrophoretic mobility shift assays were performed using an RATS probe mixed with consecutive protein eluates. Ets-2 bound to the HIV-1-LTR–RATS in a dose-dependent manner. To assess Ets-2 binding to RATS in vivo, Jurkat cells were transfected with 2× RATS-CAT and stained for the Ets-2 protein and the RATS sequence by combining immunofluorescence and fluorescence in situ hybridization techniques. In unstimulated cells, Ets-2 bound to RATS, whereas no binding was observed in stimulated cells. To test for RATS specificity, the same experiments were performed with 2× mutantRATS-CAT, and no binding of Ets-2 was observed. The results were corroborated by chromatin immunoprecipitation assays performed with the same cells. Our results show that Ets-2 is a transcriptional repressor of HIV-1. Repression of HIV-LTR-RATS mediated by Ets-2 may account for the low-level transcription and replication of HIV-1 in naive Th-cells, and contribute to the viral latency and maintenance of viral reservoirs in patients, despite long-term therapy.

HIV-1 is transcriptionally active in activated T helper (Th)-cells and inactive in naive or resting memory Th-cells. Ets-2 is a preinduction transcriptional repressor of the IL-2 gene in naive Th-cells and a candidate transcriptional repressor of HIV-1 in the same cells, because the -279 to -250 upstream region of HIV-1-LTR [repressor--activator target sequence (RATS)], that participates in HIV-1-LTR transcriptional silencing, encompasses the AAGGAG Ets-2 binding site. In this proof of concept study, we investigated whether Ets-2 represses the expression of HIV-1. To assess whether Ets-2 can repress HIV-1 transcriptional activation acting through RATS, we transfected Jurkat cells with an Ets-2 overexpression plasmid (pCDNA3-ets-2) or Ets-2 silencing plasmids (ets-2-shRNA) and, as target genes, plasmids carrying the whole HIV-1-LTR sequence (HIV-1-LTR-CAT) or two copies of the RATS sequence (2x RATS-CAT) or a point mutation in the Ets-2 binding site (2x mutantRATS-CAT) or CMV-CAT (control). Ets-2 overexpression resulted in a significant reduction of HIV-1-LTR-CAT and 2x RATS-CAT activities in stimulated cells, but not of the 2x mutantRATS-CAT or CMV-CAT. Ets-2 silencing led to increased activities of HIV-1-LTR-CAT and 2x RATS-CAT in unstimulated cells, but had no effect on the activities of 2x mutantRATS-CAT and CMV-CAT. To assess Ets-2 binding to HIV-1-LTR--RATS in naive Th-cells, we isolated naive Th-cell nuclear proteins and passed them through an Ets-2 antibody column; electrophoretic mobility shift assays were performed using an RATS probe mixed with consecutive protein eluates. Ets-2 bound to the HIV-1-LTR--RATS in a dose-dependent manner. To assess Ets-2 binding to RATS in vivo, Jurkat cells were transfected with 2x RATS-CAT and stained for the Ets-2 protein and the RATS sequence by combining immunofluorescence and fluorescence in situ hybridization techniques. In unstimulated cells, Ets-2 bound to RATS, whereas no binding was observed in stimulated cells. To test for RATS specificity, the same experiments were performed with 2x mutantRATS-CAT, and no binding of Ets-2 was observed. The results were corroborated by chromatin immuno- precipitation assays performed with the same cells. Our results show that Ets-2 is a transcriptional repressor of HIV-1. Repression of HIV-LTR-RATS mediated by Ets-2 may account for the low-level transcription and replication of HIV-1 in naive Th-cells, and contribute to the viral latency and maintenance of viral reservoirs in patients, despite long-term therapy. [ABSTRACT FROM AUTHOR]

Hormone therapy is the most effective treatment for patients with estrogen receptor α-positive breast cancers. However, although resistance occurs during treatment in some cases and often reflects changed estrogen receptor α status, the relationship between changes in estrogen receptor α expression and resistance to therapy are poorly understood. In this study, we identified a mechanism for altered estrogen receptor α expression during disease progression and acquired hormone therapy resistance in aromatase inhibitor-resistant breast cancer cell lines. Subsequently, we investigated promoter switching and DNA methylation status of the estrogen receptor α promoter, and found marked changes of methylation at a single CpG site (CpG4) in resistant cells. In addition, luciferase reporter assays showed reduced transcriptional activity from this methylated CpG site. This CpG region was also completely conserved among species, suggesting that it acts as a methylation-sensitive Ets-2 transcription factor binding site, as confirmed using chromatin immunoprecipitation assays. In estrogen receptor α-positive tumors, CpG4 methylation levels were inversely correlated with estrogen receptor α expression status, suggesting that single CpG site plays an important role in the regulation of estrogen receptor α transcription. [ABSTRACT FROM AUTHOR]

Background Atherosclerosis is a chronic immune-inflammatory disorder and one of the leading causes responsible for cardiovascular morbidity and mortality. Traditional Chinese medicine treatment with multi-targets has shown prospects for the therapeutic effect on atherosclerosis. Thus, this study aims to investigate whether xiaoxianggou has benefit for reducing the atherosclerotic plaque area in endogenous high Ang II ApoE −/− mice and investigated the underlying mechanisms. Methods Endogenous high Ang II ApoE −/− mice model was generated by using two kidney one clip (2K1C). All mice were treated by intragastric administration with xiaoxianggou two times a week for 16 weeks. En face plaque area was analyzed by oil-red O staining. Serum anti-OxLDL antibodies were measured by ELISA assay. Expression of miR-203 and Ets-2 were evaluated using qRT-RCR and western blotting analysis, respectively. Results This study revealed that xiaoxianggou treatment dose-dependently reduced the atherosclerotic plaque area and serum autoantibodies against oxLDL, elevated miR-203 expression and reduced Ets-2 expression in endogenous high Ang II ApoE −/− mice. In primary arterial ECs, Xiaoxianggou reverses the reduced miR-203 expression and the elevated Ets-2 expression induced by AngII, which was further recovered by miR-203 inhibitor. Additionally, miR-203 regulated the expression of Ets-2 by targeting Ets-2-3′ UTR. Moreover, miR-203 inhibitor reversed the reduction of atherosclerotic lesion area induced by Xiaoxianggou. Conclusions These findings present that xiaoxianggou plays an anti-atherosclerotic role in endogenous high Ang II ApoE −/− mice model, which is partly due to its antioxidant actions against atherosclerosis and the inhibition of miR-203 on the expression of Ets-2 in endothelial cells. [ABSTRACT FROM AUTHOR]

Catalysts having unprecedented selectivity toward ethane dehydrogentation were prepared by combining platinum and zinc on the surface of the titanate ETS-2. This high surface area, sodium titanate ion exchanger affords high metal dispersion, presents many active sites to the gas stream, and is free of any pore structure that can influence mass transfer to and away from the active sites. It was determined that the addition of zinc to platinum-loaded ETS-2 changes the electronic properties of the metals and significantly improves the specificity of the catalyst. By changing the zinc-to-platinum ratio, and by manipulating the space velocity of the gas, the production of side products and coke can be suppressed or eliminated. © 2015 American Institute of Chemical Engineers AIChE J, 61: 4367-4376, 2015 [ABSTRACT FROM AUTHOR]

Growth signals are directly or indirectly involved in telomerase regulation. In this study, we investigated molecular mechanisms of the effect of EGF (epidermal growth factor) on regulating hTERT (human telomerase reverse transcriptase) expression. To elucidate specific transcription factors involved in EGF-stimulated hTERT transcription in A549 and H1299 lung cancer cells, transcription factors drives hTERT promoter activity, such as Myc, Mad, and Ets-2, was evaluated on luciferase reporter assay. The upregulation of hTERT promoter by Ets-2 and Myc were abolished by Mad. Using DAPA (DNA affinity precipitation assay), Ets-2 binding to SNP (T) was stronger than Ets-2 binding to SNP (C) at −245 bp upstream of the transcription start site within the core promoter of hTERT. Ets-2 silence by siRNA decreased hTERT expression at mRNA and protein levels. The regulation of hTERT promoter by EGF/Ets-2 was diminished via the EGFR kinase signal pathway-specific inhibitors AG1478 and Iressa. Inhibitors of Erk and Akt inhibited Ets-2-activated hTERT promoter activity. These data suggested that Ets-2, a genuine cancer-specific transcription factor, is actively involved in EGFR kinase-induced hTERT overexpression pathway in lung cancer cells. Blockage of this pathway may contribute to targeted gene therapy in lung cancer. [ABSTRACT FROM AUTHOR]

Engelhard titanosilicate-1 (ETS-1), Engelhard titanosilicate-2 (ETS-2) and mesoporous manganese oxide (Meso-Mn) were synthesized, and ETS-1 and ETS-2 were firstly employed in the removal of a series of heavy metals with different valences. Characterization revealed successful synthesis of ETS-1 and ETS-2, with specific surface areas of about 120 and 220 m 2 /g, respectively. The exchange capacities for monovalent cation were calculated to be 6.70 and 8.12 mmol/g, respectively. ETS-1 and ETS-2 exhibited better performance in the removal of monovalent Ag + , divalent Cu 2+ , and trivalent Y 3+ and La 3+ . The amounts of Ag + uptake were 3.45 and 3.64 mmol/g over ETS-1 and ETS-2 respectively, with ETS-1 showing a special affinity to Ag + uptake. The maximum uptake over ETS-1 and ETS-2 were 1.41–1.52, 1.82 mmol/g for divalent cations, and 0.78–0.84, 1.16–1.20 mmol/g for most of the trivalent cations, respectively. On the contrary, Meso-Mn showed priority in Fe 3+ uptake at higher initial Fe 3+ concentration. Neither of ETS-1, ETS-2 nor Meso-Mn showed priority in trivalent Cr 3+ and tetravalent Zr 4+ removal. From the amounts of heavy metal uptake, ETS-1 and ETS-2 were suggested to be layered materials as reported. [ABSTRACT FROM AUTHOR]

It was recently reported that C1qTNF-related protein 5 (CTRP5) regulates glucose and lipid metabolism in muscle cells. However, the molecular mechanism of CTRP5 expression has not been fully investigated. In this study we demonstrate the mechanism regulating the transcription of the CTRP5 gene in muscle cells. We found that potential binding sites for transcription factors were conserved in proximal region of CTRP5 promoters in human, mouse and rat. Among these factors, Ets-2 was found to increase the promoter activity of the CTRP5 gene in C2C12 cells. Deletion of −166 to −80 in the CTRP5 promoter region significantly decreased Ets-2-induced CTRP5 promoter activity. Mutagenesis evaluation indicated that two putative Ets-2-binding sites in the CTRP5 promoter are important in CTRP5 activation. Promoter enzyme immunoassay showed that Ets-2 binds directly to two Ets-2-responsive elements at regions −166/−80 of the CTRP5 promoter. Taken together, these results suggest that Ets-2 play a key role in transcriptional regulation of CTRP5 in muscle cells. [ABSTRACT FROM AUTHOR]

Associations between p160 coactivator proteins and endocrine resistance have been described. Though thought to primarily interact with steroid receptors, the p160 proteins can also interact with non-nuclear receptor transcription factors including the MAP kinase effector proteins Ets. Here, we observed that in breast cancer cells resistant and insensitive to endocrine treatment, the growth factor EGF induced Ets-2 but not Ets-1 transcriptional regulation of the oncogene myc. Ets-2 regulation of myc was found to be reliant on the p160 proteins SRC-1 and SRC-3. In support of these molecular observations, strong associations were observed between the transcription factor, Ets-2 and its coactivator SRC-1 (P<0.01) and the target gene myc (P<0.0001) in a cohort of breast cancer patients with locally advanced disease. Expression of Ets-2, SRC-1 and c-Myc individually all associated with reduced disease-free survival (P<0.001, P<0.001 and P=0.002 respectively). There was no association between SRC-3 and disease-free survival (P=0.707). SRC-1 can utilize MAP kinase effector transcription factor Ets-2 to regulate the production of the oncogene myc. These signalling mechanisms may be important in the development of steroid resistant/independent breast cancer.Oncogene (2008) 27, 3021–3031; doi:10.1038/sj.onc.1210964; published online 3 December 2007 [ABSTRACT FROM AUTHOR]

Abstract: Autoimmune regulator (AIRE) directs the expression of self-antigens in thymus. Defects in AIRE gene cause an organ-specific autoimmune disease called autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). AIRE protein is mainly expressed in thymic medullary epithelial cells, thus implying a strict control over its expression pattern. To date, only limited information is available on mechanisms responsible for the regulation of AIRE gene. Here, we show that Ets transcription factor family members Ets-1, Ets-2, and ESE-1 have positive effect on AIRE transcription. Site-directed mutagenesis and transfection studies revealed that two of the three Ets binding sites in AIRE promoter are functional and this finding has been confirmed by the electrophoretic mobility shift assay. The AIRE promoter activity could be stimulated by phorbol myristate acetate (PMA) and this activation was further enhanced by Ets transcription factors. Our results demonstrate for the first time that AIRE gene is a downstream target for the Ets family of transcription factors. [Copyright &y& Elsevier]

Background. The protooncogenes Ets-1 and Ets-2 are involved in carcinogenesis of different tumors. Nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, has antiproliferative effects on tumor cells. The question arises whether nimesulide influences Ets-1 and Ets-2 synthesis in head and neck tumors. Methods. Expression of Ets-1 and Ets-2 was analyzed in tumor tissues by immunohistochemistry. The influence of nimesulide and an extracellular signal-regulated kinase (ERK) inhibitor on cell proliferation of two head and neck cancer cell lines and Ets-1 and Ets-2 expression was determined by automated cell counting and Western blotting, respectively. Results. Immunohistochemistry showed a high expression of Ets-1 and Ets-2 in tumor tissues. In both cell lines, Ets-1 and Ets-2 expression were reduced after 24 and 48 hours by nimesulide. Conclusion. Both Ets-1 and Ets-2 are overexpressed in head and neck cancer specimens. Inhibition of Ets-1 and Ets-2 expression in head and neck cancer cell lines by nimesulide might explain the proapoptotic property of this COX-2 inhibitor. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005 [ABSTRACT FROM AUTHOR]

Down's syndrome (DS) is characterized by mental retardation and development of Alzheimer's disease (AD). Oxidative stress and mitochondrial dysfunction are both related to neurodegeneration in DS. Several genes in chromosome 21 have been linked to neuronal death, including the transcription factor ets-2. Cortical cultures derived from normal and DS fetal brains were used to study the role of ets-2 in DS neuronal degeneration, ets-2 was expressed in normal human cortical neurons (HCNs) and was markedly upregulated by oxidative stress. When overexpressed in normal HCNs, ets-2 induced a stereotyped sequence of apoptotic changes leading to neuronal death. DS HCNs exhibit intracellular oxidative stress and increased apoptosis after the first week in culture (Busciglio and Yankner, 1995). ets-2 levels were increased in DS HCNs, and, between 7 and 14 d in vitro, DS HCNs showed increased bax, cytoplasmic translocation of cytochrome c and apoptosis inducing factor, and active caspases 3 and 7, consistent with activation of an apoptotic mitochondrial death pathway. Degeneration of DS neurons was reduced by dominant-negative ets-2, suggesting that increased ets-2 expression promotes DS neuronal apoptosis. In the human brain, ets-2 expression was found in neurons and astrocytes. Strong ets-2 immunoreactivity was observed in DS/AD and sporadic AD brains associated with degenerative markers such as bax, intracellular Aβ, and hyperphosphorylated tau. Thus, in DS/AD and sporadic AD brains, converging pathological mechanisms leading to chronic oxidative stress and ets-2 upregulation in susceptible neurons may result in increased vulnerability by promoting the activation of a mitochondrial-dependent proapoptotic pathway of cell death. [ABSTRACT FROM AUTHOR]

The myb family of genes encodes highly homologous nuclear transcription factors that play distinct roles in the development of breast, germ cells and hematoid organs. While the mechanisms associated with the regulation of these genes remain unknown, the transactivation of c-Myb was previously shown to be upregulated by transcriptional cooperation with Ets-2. The present study examines the transactivation potential of the myb gene family in cooperation with Ets-2. A-Myb and c-Myb showed similar transcriptional cooperation with Ets-2, but not with Ets-1. Interestingly, B-Myb showed no cooperative activity with Ets-2 or Ets-1. Additionally, deletion mutants of A-Myb or c-Myb, where the C-terminal negative regulatory domain was deleted, did not abrogate their ability to cooperate with Ets-2. However, the deletion mutant of B-Myb, where the C-terminal positive regulatory domain was deleted, restored its ability to cooperate with Ets-2. Furthermore, studies using a series of ‘domain-swapped’ mutants between c-Myb and B-Myb revealed that the C-terminus of B-Myb, which is responsible for the protein's transactivation potential, blocks transcriptional cooperation with Ets-2. These results suggest that the myb gene family can be differentially modulated by Ets-2, and that the C-terminus is the domain that regulates this activity. [ABSTRACT FROM AUTHOR]

ETS-2 is a member of the ETS family of transcription factors. ETS-2 was initially characterized as a nuclear oncogene and has been shown to play a role in regulation of apoptosis and cell cycle progression. Members of the ETS family display high sequence homology, thus, there is considerable controversy concerning the specificity of existing ETS-2 polyclonal antibodies that have been used to define ETS-2 function. We therefore embarked on the production of ETS-2 specific monoclonal antibodies. In this report, we describe the production and characterization of six antibodies and the localization of their target epitopes to distinct domains of the ETS-2 protein. Four antibodies are ETS-2 specific and two antibodies cross-react with ETS-1, an ETS family member with the highest amino acid sequence homology to ETS-2. This report provides a comprehensive evaluation of ETS-2 specific monoclonal antibodies verified using ETS-2 null cells. These antibodies can be used for EMSA, Western blotting, immunoprecipitation and immunofluorescence staining experiments. Collectively, these reagents are invaluable molecular tools that should help better understand the biological function of ETS-2. [Copyright &y& Elsevier]

Molecular analysis of steroid-regulated gene expression in freshly isolated human eosinophils is difficult due to the inherent high rate of spontaneous apoptosis and elevated levels of endogenous ribonucleases. To circumvent these limitations, we determined if the human eosinophilic cell line EoL-1 could serve as an in vitro model of glucocorticoid signaling. We found by optimizing growth conditions in low serum-containing media that dexamethasone (Dex) treatment of EoL-1 cells induced an apoptotic pathway that was inhibited by interleukin-5 (IL-5). Moreover, gene expression profiling using RNA from untreated EoL-1 cells and from freshly isolated human eosinophils identified 380 commonly expressed genes, including the eosinophil markers granule major basic protein, prostaglandin-endoperoxide synthase 1 and arachidonate 15-lipoxygenase. Expression profiling was performed using EoL-1 cells that had been treated with dexamethasone for 0, 4, 12, 24 and 48 h identifying 162 genes as differentially expressed. Two of the most highly upregulated genes based on expression profiling were the transcription factor Ets-2 and the MHC Class II genes (Q, R, and P). Expression of these genes in EoL-1 cells was shown to be dexamethasone-induced at the RNA and protein levels which is consistent with the known function of Ets-2 in controlling cell cycle progression and the role of MHC Class II antigens in mediating eosinophil functions. [Copyright &y& Elsevier]

Protooncogenes (PO) play a crucial role for brain biology and pathology. Only the concerted action of protooncogenes enables normal brain development. The reliable and sensitive quantification of brain PO is still holding centre stage in neurobiological research. The aim of our study was therefore the determination of PO in minute amounts of brain areas. For this purpose we decided to apply the most sensitive detection principle of competitive reverse transcriptase polymerase chain reaction using capillary electrophoresis and laser-induced fluorescence detection. We selected the PO ets-2 for our studies as this transcription factor was shown to be involved in neurodegenerative disease. As little as 10ng of total RNA each were extracted from 5 different regions of human postmortem brain and used in the assay system. Our results revealed that the ets-2 gene transcript was detectable at the atto-gram level in the brain (54.5 ± 17.7 ag/ 10 ng RNA in the occipital lobe, 34.2 ± 7.5 in temporal lobe, 40.2 ± 15.6 in the frontal lobe, 31.4 ± 15.7 in the cerebellum, and undetectably low in the parietal lobe). This is the first report at this sensitivity level providing neurobiology with a powerful analytical tool. [ABSTRACT FROM AUTHOR]

Human leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), an immunoinhibitory receptor, is expressed on most types of hematopoietic cells and some tumor cells. LAIR-1 plays an inhibitory role in immune cell maturation, differentiation, and activation. LAIR-1 is also involved in some autoimmune diseases and tumors. However, the mechanism controlling the regulation of the LAIR-1 gene is still unknown. In order to elucidate the molecular mechanisms involved in LAIR-1 regulation, in the present study, we cloned and characterized the promoter region of LAIR-1 gene using a series of truncated promoter plasmids in luciferase reporter assays. Our results show that the basic core promoter of LAIR-1 is located within the region -256/-8 relative to the translational start site. Our further studies indicate that five ETS transcription factors: ELF-1, ETV-4, ETV-3L, ETS-1 and ETS-2, can up-regulate the LAIR-1 basic promoter activity. Of these, ETS-2 is the most effective transcription factor. Moreover, ETS-2 was confirmed to interact directly with the basic promoter of LAIR-1. This study presents the first description of regions/factors capable of up-regulation the promoter activity of LAIR-1. This new knowledge contributes to understanding of the molecular mechanisms involved in LAIR-1 associated immune regulation and diseases.

Radial glia cells are the first distinguishable glial population derived from neural epithelial cells and serve as guides for migrating neurons and as neural progenitor cells in the developing brain. Despite their functional importance during neural development, the determination and differentiation of these cells remains poorly understood at the molecular level. Ets-1 and Ets-2, Ets (E26 transformation-specific) transcription factors, are vertebrate homologues of Drosophila pointed, which is expressed in a subset of glia cells and promotes different aspects of Drosophila glia cell differentiation. However, it remains unsolved that the function of Ets genes is conserved in vertebrate glia development. Here we report that Ets-1 but not Ets-2 is necessary for Xenopus radial glia formation and the activity of Ets-1 is sufficient for radial glia formation prior to neural tube closure. Furthermore, we show that Ras-MAPK (mitogen activated protein kinase) signaling, which acts as an upstream activator of Ets-1 in other biological processes, also regulates radial glia formation. A mutant form of Ets-1, which is not responsive to Ras-MAPK signaling, inhibits radial glia formation promoted by Ras-MAPK signaling. Together, our results show that Ets-1 activated by Ras-MAPK signaling promotes radial glia formation during Xenopus embryogenesis.