• Promoters of variably expressed genes lack these motifs and show stronger responsiveness to enhancers. (nature.com)
  • Fig. 4: Promoter classes correspond to enhancer responsive versus ubiquitously expressed genes. (nature.com)
  • Gene regulation in the human genome is controlled by distal enhancers that activate specific nearby promoters 1 . (nature.com)
  • Promoters of housekeeping genes contain built-in activating motifs for factors such as GABPA and YY1, which decrease the responsiveness of promoters to distal enhancers. (nature.com)
  • Directed elongation from an upstream enhancer toward a downstream gene could potentially deliver RNA polymerase II to a proximal promoter, or alternatively might function directly as a distal promoter. (nih.gov)
  • High level expression of many eukaryotic genes is achieved through the action of distal regulatory sequences or enhancers. (monash.edu)
  • Sp1 activated the distal enhancer 5-fold, GABP 3-fold, and the combination 8-fold in Schneider cells. (johnshopkins.edu)
  • Regulatory regions include promoters (proximal and distal) and enhancers. (yeastgenome.org)
  • van Arensbergen, J., van Steensel, B. & Bussemaker, H. J. In search of the determinants of enhancer-promoter interaction specificity. (nature.com)
  • One interpretation of these seemingly conflicting findings, supported by some other research, is that enhancers could have specificity for classes of promoters rather than individual promoters. (genestogenomes.org)
  • The limited number of promoter types could then confer a degree of EP specificity, while also allowing room for a EP pairing to be dependent on distance. (genestogenomes.org)
  • TIPs show variable widths (0.4-10 kb) and correlate with high CpG content and increased tissue specificity at promoters. (cipsm.de)
  • combined CAP trapper, template switching, and 5′-phosphate-dependent exonuclease digestion in RAMPAGE to maximize promoter specificity. (wikipedia.org)
  • Lis, J. Promoter-associated pausing in promoter architecture and postinitiation transcriptional regulation. (nature.com)
  • Importantly, we also identify genomic features called transcriptional initiation platforms (TIPs) that are characterized by large areas of Pol II and GTF recruitment at promoters, intergenic and intragenic regions. (cipsm.de)
  • Functional analysis of the Arabidopsis PLDZ2 promoter reveals an evolutionarily conserved low-Pi-responsive transcriptional enhancer element. (bvsalud.org)
  • This study also reports the identification and characterization of a transcriptional enhancer element that is present in the PLDZ2 promoter and able to confer Pi responsiveness to a minimal, inactive 35S promoter. (bvsalud.org)
  • Here we design a high-throughput reporter assay called enhancer × promoter self-transcribing active regulatory region sequencing (ExP STARR-seq) and applied it to examine the combinatorial compatibilities of 1,000 enhancer and 1,000 promoter sequences in human K562 cells. (nature.com)
  • Fig. 5: P2 promoters contain built-in enhancer sequences. (nature.com)
  • These regulatory modules include promoters, insulators, silencers, enhancers, promoter targeting sequences and the recently identified promoter tethering element (PTE). (nih.gov)
  • In addition, we use bioinformatic analysis across twelve Drosophila genomes to identify putative cis-regulatory sequences that may be capable of facilitating specific promoter-enhancer interactions at the bithorax complex and propose a model for their molecular function during development. (nih.gov)
  • To boost transcription of a target gene, enhancer sequences must make contact with the gene's promoter. (genestogenomes.org)
  • Mutation analysis showed that the P1BS motifs present in EZ2 are necessary but not sufficient for the enhancer function, revealing the importance of adjacent sequences. (bvsalud.org)
  • We have adapted this fundamental strategy to develop a high-throughput practical assay for the recognition of active CRMs named FIREWACh (enhancer DNA sequences which are specifically active in ESCs15 upstream of the minimal promoter within FpG5. (californiaehealth.org)
  • Taken together, this data suggests that the stage-specific factors binding the proximal globin promoters and the factors flanking the AP1/NF-E2 motif of HS2 act in synergy. (monash.edu)
  • Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells. (ca.gov)
  • Coupling genome-wide DNA methylation assays with histone mark annotation has allowed for the identification of specific epigenomic changes that affect enhancer regulatory regions, revealing an additional layer of complexity to the epigenetic regulation of gene expression. (cun.es)
  • In this review, we summarize the novel evidence for the molecular and biological regulation of DNA methylation in enhancer regions and the dynamism of these changes contributing to the fine-tuning of gene expression. (cun.es)
  • Recent years have witnessed a sea change in our understanding of transcription regulation: whereas traditional models focused solely on the events that brought RNA polymerase II (Pol II) to a gene promoter to initiate RNA synthesis, emerging evidence points to the pausing of Pol II during early elongation as a widespread regulatory mechanism in higher eukaryotes. (nature.com)
  • Regulation of apoAI processing by procollagen C-proteinase enhancer-2 and bone morphogenetic protein-1. (nih.gov)
  • Molecular mechanism of p73-mediated regulation of Hepatitis B virus core promoter/enhancer II: Implications for hepatocarcinogenesis. (iegt-rostock.de)
  • Here, we investigated the mechanism of HBV pregenomic core promoter/enhancer II (cp/EII) regulation by full-length TAp73 and its oncogenic counterpart DeltaTAp73. (iegt-rostock.de)
  • Here we describe a different method of transgene regulation by the use of the human glial ®brillary acidic protein (GFAP) promoter. (lu.se)
  • Similarly, insertion of the stage selector protein site into the β-promoter boosted enhancer activity observed with HS2 but not HS2(M). In adult erythroid MEL cells, enhancement of a linked β-promoter was significantly greater with HS2 than with HS2(M). This effect was dependent on the binding of the adult stage-specific factor, erythroid Kruppel-like factor, to the β-promoter. (monash.edu)
  • Strikingly, the majority of initiation events occur in regions with enhancer-like chromatin signatures. (nih.gov)
  • For the last 30 years, mapping chromatin accessible sites has been the gold standard method to identify the location of active regulatory elements, including promoters, enhancers, silencers, and locus control regions. (duke.edu)
  • Co-localized combinations of histone modifications ("chromatin states") have been shown to correlate with promoter and enhancer activity. (biomedcentral.com)
  • Changes in chromatin states over multiple time points ("chromatin state trajectories") have previously been analyzed at promoter and enhancers separately. (biomedcentral.com)
  • With the advent of time series Hi-C data it is now possible to connect promoters and enhancers and to analyze chromatin state trajectories at promoter-enhancer pairs. (biomedcentral.com)
  • We present TimelessFlex, a framework for investigating chromatin state trajectories at promoters and enhancers and at promoter-enhancer pairs based on Hi-C information. (biomedcentral.com)
  • We utilize time series ATAC-seq data measuring open chromatin to define promoters and enhancer candidates. (biomedcentral.com)
  • We developed an expectation-maximization algorithm to assign promoters and enhancers to each other based on Hi-C interactions and jointly cluster their feature regions into paired chromatin state trajectories. (biomedcentral.com)
  • TimelessFlex clusters time series histone modifications at promoter-enhancer pairs based on Hi-C and it can identify distinct chromatin states at promoter and enhancer feature regions and their changes over time. (biomedcentral.com)
  • Multiple lines of evidence support the idea that Pol II and nucleosomes compete for promoter binding and suggest that a crucial role of paused Pol II involves maintenance of accessible promoter chromatin architecture. (nature.com)
  • This crucial meeting is mediated by interacting proteins and the formation of chromatin loops that bring distant enhancers and promoters together. (genestogenomes.org)
  • Better promoters, enhancers, and other genetic elements have contributed to increased upstream production of proteins. (genengnews.com)
  • Genomic regulatory regions like promoters and enhancers are important players in gene expression. (biomedcentral.com)
  • Subclones of a 17-kilobase (kb) murine nentrophil elastase genomic clone were assessed for their ability to stimulate the neutrophil elastase promoter in 32D c13 myeloid cells. (johnshopkins.edu)
  • Indeed HaeIII was more likely to target promoter-proximal areas than RsaI (Fig. 2c) likely due to variations in recognition sequence GC content. (californiaehealth.org)
  • DNA methylation also reversibly regulates H3K27ac and H3K27me3 at previously identified tissue-specific enhancers. (ca.gov)
  • An element located within a DNase I-hypersensitive site (DHS) 10 kb into the first intron was previously shown to augment CFTR promoter activity in a tissue-specific manner. (duke.edu)
  • Transfection of promoter-reporter constructs demonstrated that the element displays classical tissue-specific enhancer properties and can independently recruit factors necessary for transcription initiation. (duke.edu)
  • A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. (wikidata.org)
  • We find that genome-wide DNA demethylation alters occupancy of histone modifications at both promoters and enhancers. (ca.gov)
  • For example, active promoters are enriched in histone modifications H3 lysine 27 acetylation (H3K27ac) and H3 lysine 4 di−/trimethylation (H3K4me2/3), while active enhancers are enriched in H3K27ac and histone H3 lysine 4 mono−/dimethylation (H3K4me1/2). (biomedcentral.com)
  • H3K79me2/3 controls enhancer-promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells. (iric.ca)
  • Activation is controlled by an intragenic H3K79me2/3 enhancer element (KEE) leading to increased enhancer-promoter interactions between PROM1 and the nearby gene TAPT1. (iric.ca)
  • One is that enhancers select particular promoters through specific protein-protein and protein-DNA interactions. (genestogenomes.org)
  • The other model is that the EP interactions are essentially non-specific, and the key factor in determining the relationship is the distance between the enhancer and promoter. (genestogenomes.org)
  • We have utilized the interaction between the erythroid-specific enhancer in hypersensitivity site 2 (HS2) of the human β-globin locus control region and the globin gene promoters as a model to elucidate the mechanisms governing promoter/enhancer interactions. (monash.edu)
  • Recent genome-wide DNA methylation studies have challenged this paradigm, demonstrating that DNA methylation of regulatory regions outside promoters is able to influence cell-type specific gene expression programs under physiologic or pathologic conditions. (cun.es)
  • Pausing is now recognized to be a pervasive feature of promoters in mammals and Drosophila melanogaster , and the evidence supporting this from genome-wide studies is presented. (nature.com)
  • A complex intronic enhancer regulates expression of the CFTR gene by direct interaction with the promoter. (duke.edu)
  • Remarkably, productive transcription elongation across these enhancers is predominantly in the same orientation as that of the nearest downstream gene. (nih.gov)
  • A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. (wikidata.org)
  • Using PCR generated, site-specific probes corresponding to the non-coding exons 1 and 2 and intron 2 of CHOP, rearrangements in five of seven tumors mapped to the 2.4 and 1.6 kbp PstI fragments that contain the first two exons and introns of the gene and the upstream promoter region. (lu.se)
  • We assign transcription initiation sites to 7691 protein-coding genes and find that they display features typical of eukaryotic promoters. (nih.gov)
  • Based on the overlap of transcription initiation clusters with mapped transcription factor binding sites, we define 2361 transcribed intergenic enhancers. (nih.gov)
  • Core, L. J., Waterfall, J. J. & Lis, J. T. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. (nature.com)
  • This epigenetic modification is usually grouped in regions denominated CpG islands, which frequently co-localize with gene promoters, silencing the transcription of those genes. (cun.es)
  • TimelessFlex extends our previous approach Timeless, a Bayesian network for clustering multiple histone modification data sets at promoter and enhancer feature regions. (biomedcentral.com)
  • Together, this systematic assessment of enhancer-promoter compatibility suggests a multiplicative model tuned by enhancer and promoter class to control gene transcription in the human genome. (nature.com)
  • Promoters and enhancers establish precise gene transcription patterns. (californiaehealth.org)
  • High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription. (mpg.de)
  • CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells. (johnshopkins.edu)
  • An expression vector capable of encoding full-length CCAAT/enhancer-binding protein (C/EBP) has been constructed and tested in transient transfection assays for its capacity to activate transcription from the promoter of the serum albumin gene. (johnshopkins.edu)
  • Dive into the research topics of 'CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells. (johnshopkins.edu)
  • We have used Southern blot technique to test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family, CHOP, which maps to 12q13 and is assumed to be involved in adipocyte differentiation, could be the 12q gene in question. (lu.se)
  • This enhancer also shares the cytokinin and sucrose responsive properties observed for the intact PLDZ2 promoter. (bvsalud.org)
  • We find jointly clustered promoter-enhancer pairs showing the same activation patterns on both sides but with a stronger trend at the enhancer side. (biomedcentral.com)
  • There are two general schools of thought about how enhancer-promoter (EP) pairs are defined. (genestogenomes.org)
  • Truncation of the binding site for the fetal/erythroid-specific stage selector protein in the γ-promoter abolished the additional enhancer activity of HS2. (monash.edu)
  • What does procollagen C-endopeptidase enhancer protein 2 have to do with HDL-cholesteryl ester uptake? (nih.gov)
  • Identification and expression of a novel type I procollagen C-proteinase enhancer protein gene from the glaucoma candidate region on 3q21-q24. (nih.gov)
  • Assignment of the mouse Pcolce2 gene, which encodes procollagen C-proteinase enhancer protein 2, to chromosome 9 and localization of PCOLCE2 to human chromosome 3q23. (nih.gov)
  • PCOLCE2 encodes a functional procollagen C-proteinase enhancer (PCPE2) that is a collagen-binding protein differing in distribution of expression and post-translational modification from the previously described PCPE1. (nih.gov)
  • Luciferase reporter assays demonstrated that the Adcy1 promoter is selectively activated by neuronal PAS-domain protein 2 (NPAS2)/BMAL1. (jneurosci.org)
  • DNA methylation promotes H3K27me3 deposition at bivalent promoters, while opposing H3K27me3 at silent promoters. (ca.gov)
  • DNA Methylation of Enhancer Elements in Myeloid Neoplasms: Think Outside the Promoters? (cun.es)
  • We also analyze the contribution of enhancer DNA methylation on the expression of relevant genes in acute myeloid leukemia and chronic myeloproliferative neoplasms. (cun.es)
  • The characterization of the aberrant enhancer DNA methylation provides not only a novel pathogenic mechanism for different tumors but also highlights novel potential therapeutic targets for myeloid derived neoplasms. (cun.es)
  • We have compared the enhancer activity of this core element with a synthetic enhancer lacking the factor binding sites flanking the AP1/NF-E2 motif (HS2(M)). In fetal/erythroid K562 cells, enhancement of a linked γ-promoter was significantly greater with wild-type HS2 than with HS2(M). In contrast, the increase in β-promoter activity in these cells was equivalent with either enhancer fragment. (monash.edu)
  • globin promoter or a BCL11A erythroid enhancer. (cdc.gov)
  • We identify simple rules for enhancer-promoter compatibility, whereby most enhancers activate all promoters by similar amounts, and intrinsic enhancer and promoter activities multiplicatively combine to determine RNA output ( R 2 = 0.82). (nature.com)
  • Expression vectors that encoded defective forms of C/EBP failed to activate the albumin promoter. (johnshopkins.edu)
  • The molecular mechanisms that allow enhancers to bypass insulators are not currently well understood. (nih.gov)
  • Although it's clear that enhancers increase transcription this way, the primary mechanisms by which an enhancer's target genes are defined remain a matter of debate. (genestogenomes.org)
  • This enhancer is located in the second intron of the proteinase-3 gene and so may regulate more than one gene in the myeloid protease cluster. (johnshopkins.edu)
  • Promoter cluster patterns show strong correlations with gene expression signals, whereas Hi-C signals get only slightly stronger towards activation. (biomedcentral.com)
  • However, Dr. Wurm stated that the role of these elements on the DNA level has been overemphasized, and that the principle source of increased productivity comes from better cell growth and other process-related improvements that were obtained through media modifications, productivity enhancers, and media feeds. (genengnews.com)
  • These constructs consisted of one of two enhancers plus a gfp expression reporter with or without a 2 kb spacer between the enhancer and reporter. (genestogenomes.org)
  • The nomenclature of different promoter-associated RNA polymerase II (Pol II) species is explicitly defined in an effort to provide consistency in future literature. (nature.com)
  • Moreover, mutated variants of the albumin promoter that lack the C/EBP-binding site failed to be trans-activated. (johnshopkins.edu)
  • 7948 control SNVs used for training and testing, 4044 control SNVs from HepG2, 2693 SNVs of dsQTL, 51 deSNVs and 156 enhancer SNVs in B-cells from NHGRI GWAS Catalog, 56497 GM12878 enhancer SNVs and 2029 variants in training set of dsQTL model within hotspot DHS region of non-blood cell. (lu.se)
  • ShapeGTB: the role of local DNA shape in prioritization of functional variants in human promoters with machine learning. (lu.se)
  • When the inserted sequence lacked the spacer, the inserted enhancer could compensate for this separation from natural enhancers. (genestogenomes.org)
  • However, the degree to which human enhancers and promoters are intrinsically compatible has not yet been systematically measured, and how their activities combine to control RNA expression remains unclear. (nature.com)
  • Jakobsson expression under a human GFAP (hGFAP) promoter. (lu.se)
  • When tested in cultured hepatoma cells, the C/EBP expression vector achieved potent trans-activation of the albumin promoter. (johnshopkins.edu)
  • Moreover, using chromosome conformation capture (3C) analysis, we show that this element interacts with the CFTR promoter in CFTR-expressing cells. (duke.edu)
  • The structural organization of EZ2 is conserved in the orthologous genes of at least eight families of rosids, suggesting that architectural features such as the distance between the two P1BS motifs are also important for the regulatory properties of this enhancer element . (bvsalud.org)
  • 2003). The therapeutic effects of different genes delivered by ment of the hGFAP promoter used here has been extensively studied and lentiviral vectors have been documented in a number of animal found to be up-regulated after several different stimuli both in vitro and models, both in rodents and primates, and examples include delivery in vivo in transgenic mice (Brenner et al. (lu.se)
  • Many constitutively active promoters are used to induce overexpression of exogenous genes ( Table 1 ). (genengnews.com)
  • Mutation of the Sp1-binding site reduced enhancer activity 8-fold in 32D c13 cells, and mutation of either or both Ets-binding sites reduced activity 3-4-fold. (johnshopkins.edu)
  • 2.1-kb hGFAP promoter or a 1.5-kb rat neuron-speci®c enolase (rNSE) promoter (control vector) has been described elsewhere (Jakobsson et al. (lu.se)
  • Mendelian regulatory variations including 42 enhancer, 142 promoter, 153 5' UTR, 43 3' UTR, 65 RNA gene, 3 imprinting control region, and 5 microRNA gene variations. (lu.se)
  • There are a number of hypothesized that regulating the transgene with a GFAP promoter in a different vectors that transduce cells in the brain in a slightly different viral vector would give rise to a high transgenic expression in the manner (for a review see, e.g. (lu.se)