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ECR Browser: a tool for visualizing and accessing data from comparisons of multiple vertebrate genomes
Open accessAbstract
With an increasing number of vertebrate genomes being sequenced in draft or finished form, unique opportunities for decoding the language of DNA sequence through comparative genome alignments have arisen. However, novel tools and strategies are required to accommodate this large volume of genomic information and to facilitate the transfer of predictions generated by comparative sequence alignment to researchers focused on experimental annotation of genome function. Here, we present the ECR Browser, a tool that provides easy and dynamic access to whole genome alignments of human, mouse, rat and fish sequences. This web-based tool (http://ecrbrowser.dcode.org) provides the starting point for discovery of novel genes, identification of distant gene regulatory elements and prediction of transcription factor binding sites. The genome alignment portal of the ECR Browser also permits fast and automated alignments of any user-submitted sequence to the genome of choice. The interconnection of the ECR Browser with other DNA sequence analysis tools creates a unique portal for studying and exploring vertebrate genomes.
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“Using the Evolutionarily Conserved Regions browser (35), we found that the miR-146a promoter contains two evolutionarily conserved regions, ECR1 and ECR2.”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [35]
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Basic local alignment search tool
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<tt>BLAT</tt> —The <tt>BLAST</tt> -Like Alignment Tool
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Initial sequencing and comparative analysis of the mouse genome
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The UCSC Genome Browser Database
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The Ensembl genome database project
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Whole-Genome Shotgun Assembly and Analysis of the Genome of Fugu rubripes
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Human–Mouse Alignments with BLASTZPreprint
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Oshimori, N., & Fuchs, E. V. (2012) · Cell stem cell · doi:10.1016/j.stem.2011.11.005 · Cited by 394
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“species (Ovcharenko et al., 2004).”
Genome-wide scans for footprints of natural selection
Oleksyk, T. K., Smith, M. W., & O'Brien, S. J. (2010) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2009.0219 · Cited by 340
“Selection signatures can be observed by plotting the between-species divergence of homologous segments and comparing it with the genome-wide average: phylogenetic shadowing (Mayor et al. 2000; Ovcharenko et al. 2004).”
BackgroundThe making of a melanocyte: the specification of melanoblasts from the neural crest
Thomas, A. J., & Erickson, C. A. (2008) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2008.00506.x · Cited by 271
“When we performed an in silico analysis (Ovcharenko et al., 2004) of the FoxD3 locus (Figure 5), extending upstream approximately 200 kb and downstream approximately 100 kb from FoxD3’s single intron, we discovered several ECRs containing many conserved and aligned transcription factor binding sites.”
MethodGotea, V., Visel, A., Westlund, J. M., Nobrega, M. A., Pennacchio, L. A., & Ovcharenko, I. (2010) · Genome Research · doi:10.1101/gr.104471.109 · Cited by 248
“7A) indicates a stronger association between HCTs and Ep300 than between other ECRs and Ep300.”
BackgroundMethodInfluentialSelf-citationResseguie, M., Song, J., Niculescu, M. D., da Costa, K.-A., Randall, T. A., & Zeisel, S. H. (2007) · The FASEB Journal · doi:10.1096/fj.07-8227com · Cited by 251
“We used the BLASTZbased genome alignments generated by the ECR Browser (http://ecrbrowser.dcode.org; last accessed 01/03/07) ( 34 ).”
MethodEvolution and functional classification of vertebrate gene desertsPreprint
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“org) (Ovcharenko et al. 2004a).”
Self-citationKathiresan, S., Larson, M. G., Vasan, R. S., Guo, C., Gona, P. N., Keaney, J. F., Wilson, P. W. F., Newton‐Cheh, C., Musone, S. L., Camargo, A. L., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.591271 · Cited by 229
NKX2.1 specifies cortical interneuron fate by activatingLhx6
Du, T., Xu, Q., Ocbina, P. J. R., & Anderson, S. A. (2008) · Development · doi:10.1242/dev.015123 · Cited by 220
“…using the ECR browser (http://www.dcode.org) sequence alignment and visualization tool (Ovcharenko et al., 2004b). rVISTA (http://rvista.dcode.org/) (Loots and Ovcharenko, 2004; Ovcharenko et al., 2004a) was used to identify potential transcription factor binding sites (http://zpicture.dcode.org/).”
MethodSeiler, M. P., Mathew, R. S., Liszewski, M. K., Spooner, C. J., Barr, K., Meng, F., Singh, H., & Bendelac, A. S. (2012) · Nature Immunology · doi:10.1038/ni.2230 · Cited by 228
Elnitski, L. L., Jin, V. X., Farnham, P., & Jones, S. J. M. (2006) · Genome Research · doi:10.1101/gr.4140006 · Cited by 219
“2003), and ECR browser (Ovcharenko et al. 2004) allow a user to define and extract conserved sequences from a multi-species alignment.”
BackgroundA global role for EKLF in definitive and primitive erythropoiesis
Hodge, D. J., Coghill, E., Keys, J. R., Maguire, T. L., Hartmann, B., McDowall, A. W., Weiss, M. J., Grimmond, S. M., & Perkins, A. C. (2005) · Blood · doi:10.1182/blood-2005-07-2888 · Cited by 209
Regulatory variation in a TBX5 enhancer leads to isolated congenital heart disease
Smemo, S., Campos, L. C. G., Moskowitz, I. P. G., Krieger, J. E., Pereira, A. C., & Nóbrega, M. A. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds165 · Cited by 204
Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma
Natsuizaka, M., Whelan, K. A., Kagawa, S., Tanaka, K., Giroux, V., Chandramouleeswaran, P. M., Long, A., Sahu, V., Darling, D. S., Que, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01500-9 · Cited by 203
Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers
Seo, S., Lim, J.-W., Yellajoshyula, D., Chang, L.-W., & Kroll, K. L. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601923 · Cited by 202
“We used the evolutionarily conserved region (ECR) browser to compare genomic sequences for Dll1, Ebf3, Elavl3, Gadd45g, NeuroD4 (Ath3), and HEN1 (Nhlh1) between multiple vertebrates and detect E-box containing ECRs, which represent potential enhancers (Ovcharenko et al, 2004).”
MethodSmad3 promotes cancer progression by inhibiting E4BP4-mediated NK cell development
Tang, P. M., Zhou, S., Meng, X., Wang, Q.-M., Li, C., Lian, G., Huang, X.-R., Tang, Y.-J., Guan, X., Yan, B. P.-Y., et al. (2017) · Nature Communications · doi:10.1038/ncomms14677 · Cited by 196
Thomas, A. J., & Erickson, C. A. (2009) · Development · doi:10.1242/dev.031989 · Cited by 176
“Preliminary in silico analysis (Ovcharenko et al., 2004) of the genomic FOXD3 locus revealed several evolutionary conserved regions containing binding sites for transcription factors known to be expressed in the NC.”
BackgroundComparative Analysis of Insulin Gene Promoters
Hay, C. W., & Docherty, K. (2006) · Diabetes · doi:10.2337/db06-0788 · Cited by 175
“The computational tools included CLUSTAL W (45), T-Coffee (46), GraphAlign (47), ECR Browser (48), Mulan (49), zPicture (50), TRES (51), and TRANSFAC (52).”
MethodDirect Regulation of CLOCK Expression by REV-ERB
Crumbley, C., & Burris, T. P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017290 · Cited by 165
“Using the Evolutionarily Conserved Region Browser [15], it was determined that a putative RevRE is located within the CLOCK gene that is conserved between mice and humans, as shown in Figure 1b.”
MethodTBX5 drives Scn5a expression to regulate cardiac conduction system function
Arnolds, D. E., Liu, F., Fahrenbach, J. P., Kim, G. H., Schillinger, K. J., Smemo, S., McNally, E. M., Nóbrega, M. A., Patel, V. V., & Moskowitz, I. P. G. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62617 · Cited by 164
“Ovcharenko I, Nobrega MA, Loots GG, Stubbs L. ECR Browser: a tool for visualizing and accessing data from comparisons of multiple vertebrate genomes.”
BackgroundInfluentialGenomic Perspectives of Transcriptional Regulation in Forebrain Development
Nord, A. S., Pattabiraman, K., Visel, A., & Rubenstein, J. L. R. (2015) · Neuron · doi:10.1016/j.neuron.2014.11.011 · Cited by 152
“…(homology across species) or constraint (relative local sequence conservation across evolution) (Cooper et al., 2005; Frazer et al., 2004; Ovcharenko et al., 2004; Prabhakar et al., 2006b; Schwartz et al., 2000; Siepel et al., 2005) coupled to functional screening via reporter assays…”
EPHA2 Is Associated with Age-Related Cortical Cataract in Mice and Humans
Jun, G., Guo, H., Klein, R., Klein, R., Wang, J. J., Mitchell, P., Miao, H., Lee, K. E., Joshi, T., Buck, M., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000584 · Cited by 158
“Phylogenetic footprinting [46] and phylogenetic shadowing [47] were used for additional SNP selection.”
MethodMultiple congenital anomalies-hypotonia-seizures syndrome is caused by a mutation in PIGN
Maydan, G., Noyman, I., Har‐Zahav, A., Neriah, Z. B., Pasmanik, M., Yeheskel, A., Albin‐Kaplanski, A., Maya, I., Magal, N., Birk, E., et al. (2011) · Journal of Medical Genetics · doi:10.1136/jmg.2010.087114 · Cited by 148
“Evolutionary Conserved Regions (ECR) browser analysis was performed on human genome (hg18) to show PIGN gene pairwise alignments between human and various species, as follows: spotted green pufferfish (Tetraodon nigrovoridis, tetNig1), fugu pufferfish (Takifugu rubripes, fr2), frog (Xenopus laevis, xenTro2), chicken (…”
MethodZhou, Q., Chung, A. C. K., Huang, X. R., Dong, Y., Yu, X., & Lan, H. Y. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.10.007 · Cited by 148
Talmud, P. J., Cooper, J. A., Palmen, J., Lovering, R. C., Drenos, F., Hingorani, A. D., & Humphries, S. E. (2008) · Clinical Chemistry · doi:10.1373/clinchem.2007.095489 · Cited by 146
Hodge, R. D., Nelson, B. R., Kahoud, R. J., Yang, R., Mussar, K. E., Reiner, S. L., & Hevner, R. F. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0532-12.2012 · Cited by 152
“Sox2 gene sequences were scanned for evolutionary conserved regions (ECRs) from aligned vertebrate genomes using the ECR Browser (Ovcharenko et al., 2004) as described previously (Bedogni et al.”
MethodTGF-β Mediates Renal Fibrosis via the Smad3-Erbb4-IR Long Noncoding RNA Axis
Feng, M., Tang, P. M., Huang, X., Sun, S., You, Y., Xiao, J., Lv, L., Xu, A., & Lan, H.-Y. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.09.024 · Cited by 142
Characterization of the Core Mammalian Clock Component, NPAS2, as a REV-ERBα/RORα Target Gene
Crumbley, C., Wang, Y., Kojetin, D. J., & Burris, T. P. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.129288 · Cited by 140
UCNEbase—a database of ultraconserved non-coding elements and genomic regulatory blocks
Dimitrieva, S., & Bucher, P. (2013) · Nucleic Acids Research · doi:10.1093/nar/gks1092 · Cited by 124
“Only Ancora and ECR browser offer data for a comparable number of species.”
MethodYang, X. O., Zhang, H., Kim, B. S., Niu, X., Peng, J., Chen, Y., Kerketta, R., Lee, Y., Chang, S. H., Corry, D. B., et al. (2013) · Nature Immunology · doi:10.1038/ni.2633 · Cited by 138
Predicting tissue-specific enhancers in the human genomePreprint
Pennacchio, L. A., Loots, G. G., Nóbrega, M. A., & Ovcharenko, I. (2007) · Genome Research · doi:10.1101/gr.5972507 · Cited by 135
Self-citationOosterveen, T., Kurdija, S., Alekseenko, Z., Uhde, C. W., Bergsland, M., Sandberg, M., Andersson, E., Dias, J. M. M., Muhr, J., & Ericson, J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.09.015 · Cited by 132
“The ECR browser (Ovcharenko et al., 2004) was used to screen genomic loci of”
SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub
Piazza, R., Magistroni, V., Redaelli, S., Mauri, M., Massimino, L., Sessa, A., Peronaci, M., Lalowski, M. M., Soliymani, R., Mezzatesta, C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04462-8 · Cited by 132
Tang, P. M., Zhou, S., Li, C., Liao, J., Xiao, J., Wang, Q., Lian, G., Li, J., Huang, X., To, K., et al. (2017) · Kidney International · doi:10.1016/j.kint.2017.07.026 · Cited by 130
DiRE: identifying distant regulatory elements of co-expressed genes
Gotea, V., & Ovcharenko, I. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn300 · Cited by 129
Self-citationPDGFR blockade is a rational and effective therapy for NPM-ALK–driven lymphomas
Laimer, D., Dolznig, H., Kollmann, K., Vesely, P. W., Schlederer, M., Merkel, O., Schiefer, A. I., Hassler, M. R., Heider, S., Amenitsch, L., et al. (2012) · Nature Medicine · doi:10.1038/nm.2966 · Cited by 128
Johnson, M. P., Brennecke, S. P., East, C. E., Göring, H. H. H., Kent, J. W., Dyer, T. D., Said, J. M., Roten, L. T., Iversen, A., Abraham, L. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033666 · Cited by 127
“intergenic regions were identified using the ECR Browser [62].”
MethodGenome-wide discovery of human heart enhancersPreprint
Narlikar, L., Sakabe, N. J., Blanski, A. A., Arimura, F. E., Westlund, J. M., Nóbrega, M. A., & Ovcharenko, I. (2010) · Genome Research · doi:10.1101/gr.098657.109 · Cited by 121
“All these elements are conserved between human and mouse genomes; 42% are also conserved between human and chicken genomes (with >70% identity, the default option of the ECR Browser; Ovcharenko et al. 2004).”
BackgroundMethodInfluentialSelf-citationTNF-α blockade induces IL-10 expression in human CD4+ T cells
Evans, H. G., Roostalu, U., Walter, G. J., Gullick, N., Frederiksen, K. S., Roberts, C. A., Sumner, J., Baeten, D., Gerwien, J. G., Cope, A. P., et al. (2014) · Nature Communications · doi:10.1038/ncomms4199 · Cited by 119
“Evolutionarily conserved regions (70% similarity over 100 bp) were identified with ECR Browser 57 aligned by Mulan and searched for conserved Aiolos motifs by multiTF 58, 59”
Basel‐Vanagaite, L., Zevit, N., Har‐Zahav, A., Guo, L., Parathath, S., Pasmanik‐Chor, M., McIntyre, A. D., Wang, J., Albin‐Kaplanski, A., Hartman, C., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.028 · Cited by 106
“Fam), rhesus monkey ([Macaca mulatta] rheMac) and chimpanzee ([Pan troglodytes] panTro2).(22) Structure information was obtained from the PDBSum server,(23) based on the crystal structure of GPD1.”
MethodFunction of microRNA‐375 and microRNA‐124a in pancreas and brain
Baroukh, N., & OBBERGHEN, E. V. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07353.x · Cited by 105
Fine-tuning of the intracellular canonical Notch signaling pathway
Borggrefe, T., & Liefke, R. (2012) · Cell Cycle · doi:10.4161/cc.11.2.18995 · Cited by 102
Tian, X., Jin, R. U., Bredemeyer, A. J., Oates, E. J., Błażewska, K. M., McKenna, C. E., & Mills, J. C. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01328-09 · Cited by 102
Nelson, B. R., Hartman, B. H., Ray, C. A., Hayashi, T., Bermingham‐McDonogh, O., & Reh, T. A. (2009) · Developmental Dynamics · doi:10.1002/dvdy.21848 · Cited by 94
Martin, D., Pantoja, C., Fernández‐Miñán, A., Valdes‐Quezada, C., Moltó, E., Matesanz, F., Bogdanović, O., de la Calle‐Mustienes, E., Domı́nguez, O., Taher, L., et al. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2059 · Cited by 91
“We therefore considered two CTCF sites as equivalent evolutionarily if they were syntenic in two species—that is, if they separated the same evolutionarily conserved regions (ECR”
BackgroundSelf-citationEngström, P. G., Fredman, D., & Lenhard, B. (2008) · Genome biology · doi:10.1186/gb-2008-9-2-r34 · Cited by 87
“Unlike conservation profiles, which can be seen in several other genome browsers [21,22,30,34], HCNE density plots do not directly reflect conservation on the sequence/alignment level; instead, they show density distributions of HCNEs on a larger scale.”
BackgroundOishi, K., Aramaki, M., & Nakajima, K. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515949113 · Cited by 85
“We used the ECR Browser (26) to identify conserved genomic regions between mice and humans, which often include gene regulatory elements.”
MethodRegulation of vertebrate corticotropin-releasing factor genes
Yao, M., & Denver, R. J. (2007) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2007.01.046 · Cited by 86
“Alignments were done using the evolutionary conserved region (ECR) browser (Ovcharenko et al., 2004; http://ecrbrowser.dcode.org/).”
Imaging Light Responses of Targeted Neuron Populations in the Rodent Retina
Borghuis, B. G., Tian, L., Xu, Y., Nikonov, S. S., Vardi, N., Zemelman, B. V., & Looger, L. L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6064-10.2011 · Cited by 87
“Cross-species alignment (ECR browser; ecrbrowser.decode.org) (Ovcharenko et al., 2004) of the genomic sequences flanking the mouse metabotropic glutamate receptor 1 gene (mGluR1/Grm1) using ECR setting 350/77 (length/similarity) revealed five conserved domains 200 – 600 bp in length.”
MethodHoxa2 Selectively Enhances Meis Binding to Change a Branchial Arch Ground State
Amin, S., Donaldson, I. J., Zannino, D. A., Hensman, J. J., Rattray, M., Losa, M., Spitz, F., Ladam, F., Sagerström, C. G., & Bobola, N. (2015) · Developmental Cell · doi:10.1016/j.devcel.2014.12.024 · Cited by 86
“(D) Sequence conservation of the Hoxa2 proximal promoter in vertebrates, generated by the ECR Browser (Ovcharenko et al., 2004).”
BackgroundHuman-zebrafish non-coding conserved elements act in vivo to regulate transcription
Shin, J. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki853 · Cited by 86
“Human (NCBI build 35) and zebrafish genomes were aligned, and the alignments annotated and binned as described previously (25).”
MethodResultRegulating Il9 transcription in T helper cells
Perumal, N. B., & Kaplan, M. H. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.01.006 · Cited by 87
“A comparison of sequences [14] near the murine Il9 gene with human and canine IL9 identifies two conserved non-coding sequences (CNS) 5-prime of the Il9 gene.”
Epigenetics and T helper 1 differentiation
Aune, T. M., Collins, P. L., & Chang, S. (2008) · Immunology · doi:10.1111/j.1365-2567.2008.03026.x · Cited by 83
Kinugasa, H., Whelan, K. A., Tanaka, K., Natsuizaka, M., Long, A., Guo, A. J., Chang, S., Kagawa, S., Srinivasan, S., Guha, M., et al. (2015) · Oncogene · doi:10.1038/onc.2014.449 · Cited by 81
cJun integrates calcium activity and tlx3 expression to regulate neurotransmitter specification
Marek, K. W., Kurtz, L. M., & Spitzer, N. C. (2010) · Nature Neuroscience · doi:10.1038/nn.2582 · Cited by 82
Functional Access to Neuron Subclasses in Rodent and Primate Forebrain
Mehta, P., Kreeger, L., Wylie, D. C., Pattadkal, J. J., Lusignan, T., Davis, M. J., Turi, G. F., Li, W.-K., Whitmire, M. P., Chen, Y., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.011 · Cited by 67
“To target SST + neurons, we identified a candidate regulatory domain upstream of the SST gene that was conserved between mouse and human genomes (ECR Browser, Ovcharenko et al., 2004; Figure 4A).”
Hiller, M., Agarwal, S., Notwell, J. H., Parikh, R., Guturu, H., Wenger, A. M., & Bejerano, G. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt557 · Cited by 72
“GO biological process Regulation of transcription, DNA-dependent 0 2.7 3E-314 2.0 n.d. n.d. Wiki pathways Nuclear receptors 3 E-128 5.0 5E-41 3.0 n.d. n.d. InterPro Homeodomain-like 0 3.7 5E-199 2.5 n.d. n.d. aTo exclude any differences because of our stringent filtering procedure, we applied the same filters for repe…”
MethodInfluentialMalygin, A. A., Parakhnevitch, N. M., Ivanov, A. V., Eperon, I. C., & Karpova, G. G. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm701 · Cited by 79
“Generated by the ECR browser (35) graphic plot of genomic alignment and comparative analysis with the genes coding for rpS13 in dog, mouse, rat and chicken.”
BackgroundMethodFoxc1 and Foxc2 deletion causes abnormal lymphangiogenesis and correlates with ERK hyperactivation
Fatima, A., Wang, Y., Uchida, Y., Norden, P. R., Liu, T., Culver, A. E., Dietz, W. H., Culver, F., Millay, M., Mukouyama, Y., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci80465 · Cited by 77
“using the ECR Browser (68) to compare human and mouse genomes.”
MethodInfluentialIdentification of cis-regulatory elements for MECP2 expression
Liu, J., & Francke, U. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl099 · Cited by 79
“org/), corresponding to the human May 2004 (hg17) assembly and the mouse May 2004 (mm5) assembly (53).”
BackgroundThomas, C. P., Andrews, J. I., Raikwar, N. S., Kelley, E. A., Herse, F., Dechend, R., Golos, T. G., & Liu, K. Z. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0017 · Cited by 82
Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiation
Jackson, S. J., Zhang, Z., Feng, D., Flagg, M., O’Loughlin, E., Wang, D., Stokes, N., Fuchs, E. V., & Yi, R. (2013) · Development · doi:10.1242/dev.089649 · Cited by 80
ZEB2 Shapes the Epigenetic Landscape of Atherosclerosis
Cheng, P. P., Wirka, R. C., Clarke, S. L., Zhao, Q., Kundu, R. K., Nguyen, T., Nair, S., Sharma, D., Kim, H.-J., Shi, H., et al. (2022) · Circulation · doi:10.1161/circulationaha.121.057789 · Cited by 70
ETS1 governs pathological tissue-remodeling programs in disease-associated fibroblasts
Yan, M., Komatsu, N., Muro, R., Huynh, N. C., Tomofuji, Y., Okada, Y., Suzuki, H. I., Takaba, H., Kitazawa, R., Kitazawa, S., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01285-0 · Cited by 78
Chandler, R. L., Chandler, K. J., McFarland, K. A., & Mortlock, D. P. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01609-06 · Cited by 74
“Also shown are vertebrate MultiZ alignment and conservation tracks (6) as well as ECR size and percent identity generated by the ECR browser (59).”
BackgroundMethodSex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells
Werner, R. J., Schultz, B. M., Huhn, J. M., Jelı́nek, J., Madžo, J., & Engel, N. (2017) · Biology of Sex Differences · doi:10.1186/s13293-017-0150-x · Cited by 73
Adurthi, S., Kumar, M. M., Vinodkumar, H. S., Mukherjee, G., Krishnamurthy, H., Kshitish, A. K., Bafna, U. D., Uma, D. K., Basavarajegowda, A., Krishna, S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17102-w · Cited by 78
Kagawa, S., Natsuizaka, M., Whelan, K. A., Facompre, N. D., Naganuma, S., Ohashi, S., Kinugasa, H., Egloff, A. M., Basu, D., Gimotty, P. A., et al. (2014) · Oncogene · doi:10.1038/onc.2014.169 · Cited by 73
EKLF/KLF1 Controls Cell Cycle Entry via Direct Regulation of E2f2
Tallack, M. R., Keys, J. R., Humbert, P. O., & Perkins, A. C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.006346 · Cited by 71
Sahebjada, S., Schäche, M., Richardson, A. J., Snibson, G. R., MacGregor, S., Daniell, M. D., & Baird, P. N. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12982 · Cited by 70
Bruce, S. J., Gardiner, B., Burke, L. J., Gongora, M., Grimmond, S. M., & Perkins, A. C. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-365 · Cited by 70
“Ovcharenko I, Nobrega MA, Loots GG, Stubbs L: ECR Browser: a tool for visualizing and accessing data from comparisons of multiple vertebrate genomes.”
MethodInfluentialBrunet, M. A., Levesque, S. A., Hunting, D. J., Cohen, A. A., & Roucou, X. (2018) · Genome Research · doi:10.1101/gr.230938.117 · Cited by 75
“2007) ECR Browser Conservation signal browser Identify evolutionary conserved regions (ECRs) (Ovcharenko et al. 2004) GTB SNV intolerance browser Identify regions likely intolerant for mutations (Shihab et al.”
BackgroundMIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration
Simone, R., Javad, F., Emmett, W., Wilkins, O. G., Almeida, F., Barahona‐Torres, N., Zarȩba-Pasławska, J., Ehteramyan, M., Zuccotti, P., Modelska, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03556-6 · Cited by 70
You, Y., Huang, X., Chen, H., Lyu, X., Liu, J., & Lan, H. Y. (2016) · Scientific Reports · doi:10.1038/srep26740 · Cited by 72
Local insulin-like growth factor I expression is essential for Purkinje neuron survival at birth
Croci, L., Barili, V., Chia, D. J., Massimino, L., van Vugt, R., Masserdotti, G., Longhi, R., Rotwein, P. S., & Consalez, G. G. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.78 · Cited by 65
“An evolutionary analysis of the Igf1 gene promoter (52) revealed that two putative EBF binding sites lie in a highly conserved promoter region (supplemental Fig.”
BackgroundNorden, P. R., Sabine, A., Wang, Y., Demir, C. S., Liu, T., Petrova, T. V., & Kume, T. (2020) · eLife · doi:10.7554/elife.53814 · Cited by 63
“org) (Ovcharenko et al., 2004) tool to identify conserved binding regions between the mouse and human genomes.”
BackgroundDavidson, S., Lear, M., Shanley, L. J., Hing, B. W. Q., Baizan-Edge, A., Herwig, A., Quinn, J. P., Breen, G. D., McGuffin, P., Starkey, A. J., et al. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.93 · Cited by 65
“Evolutionary conservation was identified by genomic comparison using the ECR Browser (Ovcharenko et al, 2004) and the UCSC genome browser (Kent et al, 2002).”
MethodVitamin D Related Genes, CYP24A1 and CYP27B1, and Colon Cancer Risk
Dong, L. M., Ulrich, C. M., Hsu, L., Duggan, D. J., Benitez, D. S., White, E., Slattery, M. L., Farin, F. M., Makar, K. W., Carlson, C. S., et al. (2009) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-09-0228 · Cited by 65
“To identify relevant and novel polymorphisms in CYP24A1 (chr20:52,203,395-52,223,931; 20537 bp), we sequenced the promoter region (2 kb upstream), the complete coding sequence (12 exons, including intron/exon boundaries), as well as conserved intronic regions identified by phylogenetic footprinting analysis using the…”
Mussi, P., Yu, C., O’Malley, B. W., & Xu, J. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0522 · Cited by 65
A systematic approach to identify functional motifs within vertebrate developmental enhancers
Li, Q., Ritter, D., Yang, N., Dong, Z., Li, H., Chuang, J. H., & Guo, S. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.10.019 · Cited by 63
“…cneViewer allows users to specify an anatomy and developmental timing and retrieve CNEs near genes expressed with that specificity. cneViewer was supplemented by individual inspection of CNEs using tools such as the ECRbrowser (Ovcharenko et al., 2004) and UCSC genome browser (Kent et al., 2002).”
InfluentialFunctional characterization of tissue-specific enhancers in the DLX5/6 locus
Birnbaum, R. Y., Everman, D. B., Murphy, K. K., Gurrieri, F., Schwartz, C. E., & Ahituv, N. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds336 · Cited by 63
“Identification of enhancer candidates in the minimal SHFM1 critical region using comparative genomics In order to identify enhancer candidates whose alteration could lead to SHFM1 and its associated phenotypes, we scanned the minimal SHFM1 critical region for non-coding evolutionary conserved regions (ECRs) using the…”
MethodInfluentialUpregulation of Ets1 expression by NFATc2 and NFKB1/RELA promotes breast cancer cell invasiveness
Kim, G.-C., Kwon, H., Lee, C., Verma, R. P., Rudra, D., Kim, T., Kang, K., Nam, J. H., Kim, Y., & Im, S. (2018) · Oncogenesis · doi:10.1038/s41389-018-0101-3 · Cited by 67
Lian, G., Wang, Q., Mak, T. S., Huang, X., Yu, X., & Lan, H. Y. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2021.01.006 · Cited by 64
“org/).(32,33) Then, specific primers covering the predicted Smad binding site were designed for the chromatin immunoprecipitation (ChIP) assay (Figure 6B).”
MethodRetractedStambolian, D. E., Wojciechowski, R., Oexle, K., Pirastu, M., Li, X., Raffel, L. J., Cotch, M. F., Chew, E. Y., Klein, B. E. K., Klein, R., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt116 · Cited by 63
IL-13Rα2 Membrane and Soluble Isoforms Differ in Humans and Mice
Chen, W., Sivaprasad, U., Tabata, Y., Gibson, A. M., Stier, M. T., Finkelman, F. D., & Hershey, G. K. K. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901028 · Cited by 63
Laronda, M. M., Unno, K., Ishi, K., Serna, V. A., Butler, L. M., Mills, A. A., Orvis, G. D., Behringer, R. R., Deng, C., Sinha, S., et al. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.06.024 · Cited by 63
“ECR browser (Ovcharenko et al., 2004) and VISTA enhancer browser (http://enhancer.”
BackgroundGtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon
Kayama, T., Mori, M., Ito, Y., Matsushima, T., Nakamichi, R., Suzuki, H., Ichinose, S., Saito, M., Marumo, K., & Asahara, H. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00950-15 · Cited by 63
Milne, R. L., Ribas, G., González‐Neira, A., Fagerholm, R., Salas, A., González, E., Dopazo, J., Nevanlinna, H. A., Robledo, M., & Benitez, J. J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1418 · Cited by 61
“For the latter, human DNA sequence was compared with that of other species using ECR Browser (32), 9 which aligns nucleotide sequences using FASTA and screens for evolutionary conserved regions, defined as fragments of at least 200 bp with similarity >75%.”
MethodInfluentialIL-36γ drives skin toxicity induced by EGFR/MEK inhibition and commensal Cutibacterium acnes
Satoh, T. K., Mellett, M., Meier-Schiesser, B., Fenini, G., Otsuka, A., Beer, H., Rordorf, T., Maul, J., Hafner, J., Navarini, A. A., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci128678 · Cited by 65
Pitx1 broadly associates with limb enhancers and is enriched on hindlimb cis-regulatory elements
Infante, C. R., Park, S., Mihala, A. G., Kingsley, D. M., & Menke, D. B. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.11.017 · Cited by 60
Association of the Hepatocyte Growth Factor Gene with Keratoconus in an Australian Population
Sahebjada, S., Schäche, M., Richardson, A. J., Snibson, G. R., Daniell, M. D., & Baird, P. N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084067 · Cited by 60
“org) [32], enhancer element detection using the VISTA Enhancer Browser (http://enhancer.”
MethodChia, D. J., Varco-Merth, B., & Rotwein, P. S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.117697 · Cited by 59
Mehlem, A., Palombo, I., Wang, X., Hagberg, C. E., Eriksson, U., & Falkevall, A. (2016) · Diabetes · doi:10.2337/db15-1231 · Cited by 60
“To identify putative ERR-a binding sites in the Vegfb promoter, the murine genomic sequence was analyzed by the ECR Browser, Mulan, and multiTF algorithms (9,12).”
MethodMartinez, A. F., Abe, Y., Hong, S., Molyneux, K., Yarnell, D. S., Löhr, H., Driever, W., Acosta, M. T., Arcos‐Burgos, M., & Muenke, M. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.06.026 · Cited by 61
Etsrp/Etv2 Is Directly Regulated by Foxc1a/b in the Zebrafish Angioblast
Veldman, M. B., & Lin, S. (2011) · Circulation Research · doi:10.1161/circresaha.111.251298 · Cited by 58
SOST/Sclerostin improves posttraumatic osteoarthritis and inhibits MMP2/3 expression after injury
Chang, J. C., Christiansen, B. A., Murugesh, D. K., Sebastian, A., Hum, N. R., Collette, N. M., Hatsell, S., Economides, A. N., Blanchette, C. D., & Loots, G. G. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3397 · Cited by 58
“NF-kB binding sites in hg19 coordinates were mapped to mm10 using ECR browser((27)) and conserved binding sites were identified.”
MethodSelf-citationATAC-Seq Reveals an Isl1 Enhancer That Regulates Sinoatrial Node Development and Function
Galang, G., Mandla, R., Ruan, H., Jung, C., Sinha, T., Stone, N. R., Wu, R. S., Mannion, B. J., Allu, P. K. R., Chang, K. C., et al. (2020) · Circulation Research · doi:10.1161/circresaha.120.317145 · Cited by 57
Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution
Aldea, D., Atsuta, Y., Kokalari, B., Schaffner, S. F., Prasasya, R. D., Aharoni, A., Dingwall, H. L., Warder, B. N., & Kamberov, Y. G. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2021722118 · Cited by 53
Metadata
- Authors
- Ovcharenko, I., Nobrega, M. A., Loots, G. G., & Stubbs, L.
- Affiliations
- Lawrence Livermore National Laboratory (US)
- Corresponding author
- Ovcharenko, I.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07-01
- Volume
- 32
- Issue
- Web Server
- Pages
- W280-W286
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC441493
- OpenAlex
- W1981101983
- Cited by
- 519
- References
- 32
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 13 · 2021: 32 · 2020: 23 · 2019: 19 · 2018: 27 · 2017: 21 · 2016: 24 · 2015: 21 · 2014: 23 · 2013: 42 · 2012: 40
- FWCI
- 8.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of North Texas Digital Library (University of North Texas) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- U.S. Department of Energy (W-7405, -7405-ENG-48)
- Biological and Environmental Research
- Lawrence Livermore National Laboratory (W-7405-ENG 48, -7405-Eng-48)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genetics, Bioinformatics, and Biomedical Research
- Keywords
- vertebrate genomes, gene discovery, gene regulatory elements, transcription factor binding site prediction, genome annotation
- MeSH terms
- Animals, Binding Sites, Computer Graphics, Fishes, Humans, Regulatory Sequences, Nucleic Acid, Software, Transcription Factors, Sequence Alignment, Genome, Sequence Analysis, DNA, Systems Integration, Internet, Genomics, Synteny, Mice, Rats
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