• We studied 28 genes that are expressed primarily in endothelial cells, another 28 genes that are expressed highly, but not exclusively, in cultured endothelial cells, and three control sets, consisting of genes not expressed in endothelium, genes expressed in neural tissues and housekeeping genes. (duke.edu)
  • Here, it is demonstrated that TGFβ facilitates Tβ4 expression and leads to the activation of myocardin-related transcription factors (MRTF), which are coactivators of serum response factor (SRF) and regulate the expression of genes critical for the epithelial-mesenchymal transition (EMT) and tumor metastasis. (aacrjournals.org)
  • In particular, mutations in DNA binding sites recognized by transcription factors can alter regulator binding affinities and, consequently, expression of target genes. (biomedcentral.com)
  • These ATG genes are highly conserved in mammalian cells, allowing to study their functions also in higher eukaryotes [ 1 - 4 ]. (hindawi.com)
  • To exert stimulatory or repressive effects on transcription, accessible regulatory DNA elements must be in close spatial proximity to susceptible genes. (biomedcentral.com)
  • Enhancers promote transcription by providing a binding platform for transcription factors [ 12 ] that can act on (distal) target genes through three-dimensional chromatin looping [ 13 - 15 ]. (biomedcentral.com)
  • For example, steroid and thyroid hormones directly bind to nuclear receptors, which induce expression of specific genes. (intechopen.com)
  • This protein forms a tetrameric complex with the alpha subunit, and stimulates transcription of target genes. (nih.gov)
  • ASXL1 MT are further associated with de novo accessibility of distal enhancers binding ETS transcription factors, targeting important leukemogenic driver genes. (nature.com)
  • In genomic pathway, AR transported into the cellular nucleus, bind to chromatin and control the expression of target genes [ 1 ]. (oncotarget.com)
  • Cis-acting DNA sequences which can increase transcription of genes. (lookformedical.com)
  • Candidate genes showing distinctive expression patterns in response to ethanol were clustered by pattern and further analyzed for related function, pathway membership and common transcription factor binding within and across clusters. (biomedcentral.com)
  • Moreover, transcription factors and their target genes form vast interacting gene regulatory networks which can be exquisitely stable. (amegroups.org)
  • Genes having at least one occurrence of the highly conserved motif M129 RRAGTTGT in the regions spanning 4 kb centered on their transcription starting sites [-2kb,+2kb]. (gsea-msigdb.org)
  • It is thought that interactions with other proteins (eg: Modulator of the activity of Ets called Mae) is one way in which specific binding to DNA is achieved. (wikipedia.org)
  • This is the first study describing the production and distribution of ETS-1 and ETS-2 mRNAs and proteins using in situ hybridization and immunohistochemistry in murine ocular tissue sections of normal control eyes and tumoral eyes from mice of the same age. (molvis.org)
  • In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. (embl.de)
  • Residues that compose the RNA-binding surface are conserved in a subgroup of SAM domain-containing proteins, suggesting that the function of the domain is conserved from yeast to humans. (embl.de)
  • The process of canonical autophagy follows a hierarchical-ordered recruitment of autophagy-related (ATG) proteins to the phagophore assembly site [ 5 ]. (hindawi.com)
  • Interestingly, recent data suggest a function for ULK1 not only during autophagy activation but also during elongation and closure of the autophagosomal membrane via binding to ATG8 proteins [ 8 ]. (hindawi.com)
  • The others are the site-specific TFs or the DNA sequence-specific binding proteins. (intechopen.com)
  • Protein-DNA interaction is very important for the functions of TFs, high-mobility group (HMG) and other DNA binding proteins (such as histones, DNA methyltransferases, polymerases, topoisomerases, etc . (computabio.com)
  • DNA binding domain (DBD) is often highly conserved among homologous proteins in the protein family. (computabio.com)
  • These results indicate that Tα3-Tα4 itself is not sufficient to impart a developmental delay to a chimeric "early" enhancer, and indicate the need for functional collaboration between Tα2 runx/ets sites binding proteins and proteins bound to Tα3-Tα4 for proper developmental activation. (aai.org)
  • The results showed that the ancestral proteins created weaker bonds between them compared to more 'modern' ones, and were more flexible even when bound together. (elifesciences.org)
  • A method for determining the sequence specificity of DNA-binding proteins. (lookformedical.com)
  • A method for determining points of contact between interacting proteins or binding sites of proteins to nucleic acids. (lookformedical.com)
  • Proteins which bind to DNA. (lookformedical.com)
  • The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. (lookformedical.com)
  • Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. (lookformedical.com)
  • The Dl and Twist proteins appear to make synergistic contact with the basal transcription complex, so that snail is activated throughout the presumptive mesoderm in response to both peak and high levels of the Dl gradient. (sdbonline.org)
  • Scholars@Duke publication: Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifs. (duke.edu)
  • Here we present analysis of transcription factor binding motifs co-localized with non-coding variants. (biomedcentral.com)
  • Such stability of binding motifs is even more exhibited in DNase accessible regions. (biomedcentral.com)
  • Further analysis of transcription factors with conserved binding motifs can reveal cell regulatory pathways crucial for the survivability of various human cancers. (biomedcentral.com)
  • In particular, methods that search for sequence matches to known binding motifs tend to predict many non-functional binding sites because they fail to take into consideration the biological state of the cell. (biomedcentral.com)
  • In recent years, genome-wide studies have generated a lot of data that has the potential to improve our ability to identify functional motifs and binding sites, such as information about chromatin accessibility and epigenetic states in different cell types. (biomedcentral.com)
  • Still, the reason why motif discovery is so difficult in the first place is that binding motifs are often rather short and can vary substantially between binding sites. (biomedcentral.com)
  • The promoter analysis yields 174 candidate motifs, including most previously known transcription-factor binding sites and 105 new motifs. (gsea-msigdb.org)
  • In the field of molecular biology, the ETS (E26 transformation-specific or E-twenty-six. (wikipedia.org)
  • Erythroblast Transformation Specific)) family is one of the largest families of transcription factors and is unique to animals. (wikipedia.org)
  • The ETS (Erythroblast Transformation Specific)family is divided into 12 subfamilies, which are listed below: All ETS (Erythroblast Transformation Specific) family members are identified through a highly conserved DNA binding domain, the ETS domain, which is a winged helix-turn-helix structure that binds to DNA sites with a central GGA(A/T) DNA sequence. (wikipedia.org)
  • Translocation of EWSR1 (Ewing sarcoma breakpoint region 1) with an ETS (E26 transformation-specific) transcription factor gene occurs in more than 95% of Ewing sarcomas. (medscape.com)
  • The human ETS (E26 Transformation-Specific) protein family is a diverse group of 27 known transcription factors that regulate such varied cellular processes as differentiation and apoptosis, but also appear to induce oncogenesis when mutated or aberrantly expressed [ 1 - 4 ]. (biomedcentral.com)
  • It was observed that CDK8-CycC positively regulates transcription activated by Mad (Mothers against dpp) , the primary transcription factor downstream of the Dpp/TGFβ signaling pathway . (sdbonline.org)
  • Dorsoventral (DV) patterning of the Drosophila embryo is initiated by a broad Dorsal (Dl) nuclear gradient, which is regulated by a conserved signaling pathway that includes the Toll receptor and Pelle kinase. (sdbonline.org)
  • Multiple ETS factors have been found to be associated with cancer, such as through gene fusion. (wikipedia.org)
  • In addition, ETS factors, e.g. the vertebrate Etv1 and the invertebrate Ast-1, have been shown to be important players in the specification and differentiation of dopaminergic neurons in both C. elegans and olfactory bulbs of mice. (wikipedia.org)
  • ETS factors act as transcriptional repressors, transcriptional activators, or both. (wikipedia.org)
  • This motif contains the core element of binding sites from the Ets family of transcription factors. (duke.edu)
  • The role of two members of the ETS (E26 avian leukemia oncogene) family of transcription factors, ETS-1 and ETS-2, has been investigated in many cancers but has not yet been studied in ocular tumors. (molvis.org)
  • Cancer somatic mutations in binding sites of selected transcription factors have been found under positive selection. (biomedcentral.com)
  • For many transcription factors, including multiple members of FOX, HOX, and NR families, we show that human cancers accumulate fewer mutations than expected by chance that increase or decrease affinity of predicted binding sites. (biomedcentral.com)
  • These findings are significant, since they provide novel molecular insights into the functions of ETS transcription factors in mammary cell transformation. (biomedcentral.com)
  • Binding of sequence-specific transcription factors and associated chromatin-modifying enzymes can induce post-translational modification of histone tails and can facilitate nucleosome removal [ 3 - 5 ], which can turn functional sequences such as promoters and enhancers into active, nucleosome-depleted sites [ 2 ]. (biomedcentral.com)
  • Recent global analyses of gene transcripts revealed that specific transcription factors (TFs) and their networking systems physiologically correspond to the onset of human diseases, including cancer. (intechopen.com)
  • Transcription factors are divided into two groups. (intechopen.com)
  • First, the general TFs (GTFs), including preinitiation complex components TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and THIIH, are the primary protein factors that are required for the initiation of transcription from the TATA box (or TATA element), then elongation is executed by RNA polymerase II (RNA pol II) [ 1 ]. (intechopen.com)
  • Transcription factors (TFs) are the main carcinogenic factors of many cancers, and are therefore regarded as therapeutic targets with high research value. (computabio.com)
  • Despite these difficult obstacles, with the advancement of computing power and experimental technology, and the increase in available structure data for transcription factors, structure-based drug design methods, such as molecular docking, have become more and more important in research. (computabio.com)
  • Note: In August, 2008, the nomenclature of the GA binding protein transcription factors was clarified. (nih.gov)
  • These experiments indicated that Tα3-Tα4 collaborates with factors bound to Tα1-Tα2 for the strict developmental regulation of Tcra rearrangement. (aai.org)
  • MotifLab supports comprehensive motif discovery and analysis by allowing users to integrate several popular motif discovery tools as well as different kinds of additional information, including phylogenetic conservation, epigenetic marks, DNase hypersensitive sites, ChIP-Seq data, positional binding preferences of transcription factors, transcription factor interactions and gene expression. (biomedcentral.com)
  • However, transcription factors seldom operate alone but work in concert with other transcription factors and co-factors in order to achieve the required regulatory control. (biomedcentral.com)
  • This complex process is regulated by the interplay of transcription factors with a chromatin environment, both of which provide the epigenetic information maintaining cell-type specific gene expression patterns. (amegroups.org)
  • In this review, we highlight the main signals and transcription factors and how they are integrated at the level of chromatin programming and gene expression control. (amegroups.org)
  • We also highlight recent studies identifying the cis -regulatory elements such as enhancers at the global level and explain how their developmental activity is regulated by the cooperation of cell-type specific and ubiquitous transcription factors with extrinsic signals. (amegroups.org)
  • The activity of these elements is controlled by transcription factors (TFs) which bind to DNA wrapped into chromatin, leading to the modification of the chromatin landscape, and the assembly of the transcription machinery. (amegroups.org)
  • ETS-1 and ETS-2 mRNA and protein levels were much higher in the ocular tissues of Tyrp-1-TAg mice than in control ocular tissues from wild-type mice. (molvis.org)
  • Smaug, a protein that helps to establish a morphogen gradient in Drosophila embryos by repressing the translation of nanos (nos) mRNA, binds to the 3' untranslated region (UTR) of nos mRNA via two similar hairpin structures. (embl.de)
  • Anteroposterior patterning in Drosophila melanogaster is dependent on the sequence-specific RNA-binding protein Smaug, which binds to and regulates the translation of nanos (nos) mRNA. (embl.de)
  • Molecular mechanisms of the initiation of transcription from TATA box have been well known as the most essential nuclear events in mammalian cells. (intechopen.com)
  • DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. (lookformedical.com)
  • Possible applications of the program include display of transcription factor binding sites in a genomic context or the visualisation of structural domain assignments in protein sequences and many more. (biomedcentral.com)
  • Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes. (lookformedical.com)
  • These stripes are regulated by a 300-bp enhancer (NEE) that contains high-affinity Dl-binding sites, Twist-binding sites, and "generic" E-box sequences that appear to bind ubiquitously distributed bHLH activators (Daughterless and Scute), which are present in the unfertilized egg. (sdbonline.org)
  • Desogestrel binds intracellular progesterone receptors in progesterone responsive tissue and the resultant complex interacts with DNA and results in either gene transcription or gene repression. (medindex.am)
  • Upon binding of their respective ligands and activation, intracellular signalling cascades, often involving phophorylation are induced which eventually terminate at inducible TFs and regulate their activity. (amegroups.org)
  • BRCA2 gene promoter has bi-directional activity, expressing BRCA2 and a novel C4-type zinc finger containing transcription factor ZAR2. (biomedcentral.com)
  • Ecdysone binds to the Ecdysone Receptor (EcR), which heterodimerizes with Ultraspiracle (USP), an ortholog of the vertebrate Retinoid X Receptor (RXR). (sdbonline.org)
  • In an effort to identify elusive regulators of nephron segmentation, our lab conducted a high-throughput drug screen using a bioactive chemical library and developing zebrafish, which are a conserved vertebrate model and particularly conducive to large-scale screening approaches. (mdpi.com)
  • Here we present MotifLab, a general workbench for analysing regulatory sequence regions and discovering transcription factor binding sites and cis -regulatory modules. (biomedcentral.com)
  • The targets mainly include androgen receptor (AR), ETS-related gene (ERG), MYC, thymocyte selection-associated high mobility group box protein TOX, topoisomerase II (Top2), as well as signal transducer and activator of transcription 3 (STAT3). (computabio.com)
  • The androgen receptor (AR) is a ligand-dependent transcription factor that promotes prostate cancer (PC) cell growth through control of target gene expression. (oncotarget.com)
  • Our receptor-ligand interaction analysis reveals a highly complex interactive network of the NB microenvironment from which we highlight several interactions that we suggest for future therapeutic studies. (pklab.org)
  • The protein-DNA interaction surface is different from the ligand binding pocket, that is directly exposed to the solvent. (computabio.com)
  • AR is a ligand-dependent transcription factor. (oncotarget.com)
  • DNA cleavage is inhibited where the ligand binds to DNA. (lookformedical.com)
  • Since then several milestones have been achieved in understanding this complex and highly conserved developmental process. (biomedcentral.com)
  • In this work, we integrated somatic mutations, transcription, (hydroxy)methylation, histone modifications, and chromatin accessibility to reveal the complexity of the epigenetic landscape, the simultaneous presence of multiple regulatory mechanisms affecting drivers of leukemogenesis, and remodeling of the enhancer landscape as an important driver of intratumoral heterogeneity. (nature.com)
  • In the G0/G1 growth phase ZAR2 is predominantly located inside the nucleus of the breast cells, binds to the BRCA2 promoter and inhibits the expression of BRCA2. (biomedcentral.com)
  • ZAR2 binds to BRCA2/ZAR2 bi-directional promoter in vivo and is responsible, at least in part, for the silencing of BRCA2 gene expression in the G0/G1 phase in human breast cells. (biomedcentral.com)
  • The zen promoter region contains high-affinity Dl-binding sites and closely linked "corepressor" sites. (sdbonline.org)
  • Our data demonstrate negative selection against binding sites alterations and suggest that such selection pressure protects cancer cells from rewiring of regulatory circuits. (biomedcentral.com)
  • The ER81 ETS protein, for example, is activated in human breast cancer cells by the oncoprotein HER-2, resulting in over-expression of the prosurvival telomerase reverse transcriptase (hTERT) gene [ 6 ]. (biomedcentral.com)
  • While their expression tends to be lower than protein-coding mRNAs, lncRNAs are thought to be highly expressed in a subset of cells in a population 6 . (nature.com)
  • Androgen-bound ARs exerts both genomic action and non-genomic action in PC cells. (oncotarget.com)
  • B lymphocyte development is a highly ordered process pro- expression analysis without the use of intermediate amplifica- ceeding from the progenitor cells in the bone marrow (BM) to tion steps. (lu.se)
  • Using semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blots experiments, we compared changes in ETS-1 and ETS-2 expression, their protein levels, and the regulation of some of their target gene expressions at different stages of the ocular tumoral progression in the transgenic mouse model, Tyrp-1-TAg, with those in normal eyes from control mice of the same age. (molvis.org)
  • Here, we investigated the function of E74-like factor 4 (ELF4), an ETS family member, in facilitating CRC progression. (thno.org)
  • Pimecrolimus binds to the receptor macrophilin-12 (FKBP-12) forming a complex that blocks the calcium-dependent signal transduction cascade mediated by calcineurin. (medindex.am)
  • We examined a panel of prolactin-induced tumors for characteristics relevant to clinical tumors: histotype, ERα/progesterone receptor (PR) expression and estrogen responsiveness, Activating Protein 1 (AP-1) components, and phosphorylation of signal transducer and activator of transcription 5 (Stat5), extracellular signal regulated kinase (ERK) 1/2 and AKT. (biomedcentral.com)
  • These results suggest that CDK8 and CycC, together with a few other subunits of the MED complex, may coordinate with other transcription cofactors in regulating Mad-dependent transcription during wing development in Drosophila. (sdbonline.org)
  • Drosophila has been a powerful system for deciphering the conserved mechanisms that regulate hormone signaling, sugar and lipid homeostasis, and the molecular mechanisms underlying the nutritional regulation of development. (sdbonline.org)
  • Other domains are also present and vary from ETS member to ETS member, including the Pointed domain, a subclass of the SAM domain family. (wikipedia.org)
  • The ETS family is present throughout the body and is involved in a wide variety of functions including the regulation of cellular differentiation, cell cycle control, cell migration, cell proliferation, apoptosis (programmed cell death) and angiogenesis. (wikipedia.org)
  • Amongst members of the ETS family, there is extensive conservation in the DNA-binding ETS domain and, therefore, a lot of redundancy in DNA binding. (wikipedia.org)
  • The RNA-binding SAM domain of Smaug defines a new family of post-transcriptional regulators. (embl.de)
  • Alternative translocations include EWS-ERG t(21;22), EWS-ETV t(7;22), and EWS-FEV t(2;22), all of which involve the ETS family protein. (medscape.com)
  • The ETS family transcription factor ESE-1 is often overexpressed in human breast cancer. (biomedcentral.com)
  • We are currently pursuing studies of the dominant signaling and gene regulatory networks that control this process, including the Ras/MAPK cascade, which is required for stem cell-mediated self-renewal and the p53 transcription factor family member, p63, which is required for epidermal differentiation. (stanford.edu)
  • We show here that the SAM domain of Saccharomyces cerevisiae Vts1 binds RNA with the same specificity as Smaug and that Vts1 induces transcript degradation through a mechanism involving the cytoplasmic deadenylase CCR4. (embl.de)
  • The catalytic Zn 2+ ion and Ca 2+ ion that stabilizes the relationship between the Cat and Fib domains are tightly bound within their defined pockets. (mdpi.com)
  • The compact enhanceosome created on Tα1-Tα2 explained the molecular basis for requirement of intact Tα2 TCF/LEF and ets sites for enhancer function. (aai.org)
  • This enhancer contains a cluster of low-affinity Dl binding sites that restrict expression to the ventral-most regions of early embryos. (sdbonline.org)
  • A synthetic enhancer containing high-affinity Dl-binding sites and Twist binding sites exhibits expression in this region. (sdbonline.org)
  • Nonetheless, concentrations were higher in the ETS population for cotinine, trans-3′hydroxycotinine, 3-EP, 3-deazaneplanocin A BUT and most high molecular weight PAR, whilst 2-hydroxyphenanthrene, 3 + 4-hydroxyphenanthrene and 1-hydroxyphenanthrene were only higher in the high-ETS subpopulation. (alkpathway.com)
  • Their binding to DNA inhibits synthesis of nucleic acids. (lookformedical.com)
  • A cytotoxic polypeptide quinoxaline antibiotic isolated from Streptomyces echinatus that binds to DNA and inhibits RNA synthesis. (lookformedical.com)
  • We assessed the expression of PGRN in both groups using immunohistochemistry, quantitative-reverse transcription-polymerase chain reaction (qRT-PCR), and western blotting (WB). (bvsalud.org)
  • Analysis showed function-based networks, shared transcription factor binding sites and signaling pathways for members of the clusters. (biomedcentral.com)
  • samples of non-occupationally exposed non-smoker adult subjects and to establish relationships between airborne exposures and urinary concentrations in order to (a) assess the suitability of the studied metabolites as biornarkers of PAH and ETS, (b) study the use of 3-ethenypyridine as ETS tracer and (c) link ETS scenarios with exposures to carcinogenic PAH and VOC. (alkpathway.com)
  • The seven chromosome pairs of KJJ81 subgenomes exhibit highly conserved synteny, indicating a very recent hybridization event. (biomedcentral.com)
  • The motif does not match any known transcription factor binding site. (gsea-msigdb.org)
  • Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C) , two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. (sdbonline.org)
  • Computational motif discovery for transcription factor binding sites is a challenging research problem that has been studied for many years, but we are still missing approaches that can ensure generally good performance. (biomedcentral.com)
  • We also reflect on one of the earliest realizations made in this area of study: that hematopoiesis is evolutionarily conserved, and as a consequence we reflect on the impacts of early and current discoveries and their clinical implications. (biomedcentral.com)
  • To survey the epigenetic landscape of human CMML, we interrogated mutational spectrum, transcription, DNA methylation, histone modifications, and chromatin accessibility in ASXL1 MT ( n = 8) and ASXL1 WT ( n = 8) CMML (Fig. 1a ). (nature.com)
  • While previous publications have established ESE-1's transcription factor function, we have reported that ESE-1 initiates transformation of MECs via a novel non-nuclear, non-transcriptional mechanism [ 13 ]. (biomedcentral.com)
  • Using homology modeling and site-directed mutagenesis, we have localized the RNA-binding surface of the Smaug SAM domain and have elaborated the RNA consensus sequence required for binding. (embl.de)
  • CDK8 can directly interact with Mad in vitro through the linker region between the DNA-binding MH1 (Mad homology 1) domain and the carboxy terminal MH2 (Mad homology 2) transactivation domain. (sdbonline.org)
  • The type II target gene snail contains a series of low-affinity Dl-binding sites, as well as binding sites for the bHLH activator, Twist. (sdbonline.org)
  • There were not many significant correlations between either personal exposures to PAH and their urinary metabolites, or of the latter with ETS markers. (alkpathway.com)
  • To assess the role of NES2 in regulating ESE-1 subcellular localization and subsequent transformation potency, we site-specifically mutagenized NES2, within full-length GFP-ESE-1 and GFP-NES2-SAR reporter constructs. (biomedcentral.com)
  • In this chapter, revisiting known TFs, we would argue if transcription controlling strategies could contribute for the novel therapies on human diseases. (intechopen.com)
  • Cell growth, cell proliferation and differentiation are tightly regulated and highly interconnected during development. (silverchair.com)
  • Besides CDK8 and CycC, further analyses of other subunits of the MED complex have revealed six additional subunits that are required for Mad-dependent transcription in the wing discs: Med12, Med13, Med15, Med23, Med24, and Med31. (sdbonline.org)
  • The translatability of these experiments across different biological systems such as in Xenopus laevis and Danio rerio also demonstrates that this process is conserved across several species [ 2 , 7 - 9 ]. (biomedcentral.com)