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genes, pubmed, target, breast, estrogen, article, google, scholar, cas, expression, human, gene, cells, data, figure, direct, ere, cancer, response, eres, cell, receptor, sites, analysis, putative, treatment, ici, transcriptional, mcf, profiles, control, mouse, regions, chx, conserved, estrogenresponsive, study, microarray, elements, additional, tumors, binding, predicted, file, tumor, enrichment, genome, studies, lines, sequences,

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poly-l-lysine-coated glass slides article download pdf estrogen-responsive gene-expression profiles article number r66 high-density dna microarrays estrogen receptor-regulated transcription early estrogen-induced gene liver-x-receptor alpha protein a-sepharose beads suggests context-dependent regulation ncbi gene-centered resources cis-regulatory element mapping assessing cis-regulatory elements tailed paired t-test global gene-expression profile p36d1-p34cdk4 complex activation orthologous mouse-human pairs mouse-human orthologous pairs estrogen-responsive pathways represent full size image putative er-regulated genes anti-gst antibody control c-myc proto-oncogene potential confounding factors control anti-gst products hormone-responsive breast cancer er status-dependent manner human-mouse ortholog determinations direct estrogen-responsive genes direct estrogen-response genes estrogen receptor/sp1 complexes estrogen-induced expression profiles potential er-binding site putative target gene estrogen-responsive pathways account direct er-responsive genes cross-cell line analysis potential er-binding sites t-47d cells show receptor-positive molecular signature semi-quantitative pcr analysis c-myc oncogene expression core ere half-sites genome-wide expression patterns performed high-resolution time unrelated stem-cell studies hormone-sensitive gene expression vivo formaldehyde cross-linking estrogen-regulated genes expressed mock-treated cells displayed

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         headline:Discovery of estrogen receptor α target genes and response elements in breast tumor cells
         description:Estrogens and their receptors are important in human development, physiology and disease. In this study, we utilized an integrated genome-wide molecular and computational approach to characterize the interaction between the activated estrogen receptor (ER) and the regulatory elements of candidate target genes. Of around 19,000 genes surveyed in this study, we observed 137 ER-regulated genes in T-47D cells, of which only 89 were direct target genes. Meta-analysis of heterogeneous in vitro and in vivo datasets showed that the expression profiles in T-47D and MCF-7 cells are remarkably similar and overlap with genes differentially expressed between ER-positive and ER-negative tumors. Computational analysis revealed a significant enrichment of putative estrogen response elements (EREs) in the cis-regulatory regions of direct target genes. Chromatin immunoprecipitation confirmed ligand-dependent ER binding at the computationally predicted EREs in our highest ranked ER direct target genes, NRIP1, GREB1 and ABCA3. Wider examination of the cis-regulatory regions flanking the transcriptional start sites showed species conservation in mouse-human comparisons in only 6% of predicted EREs. Only a small core set of human genes, validated across experimental systems and closely associated with ER status in breast tumors, appear to be sufficient to induce ER effects in breast cancer cells. That cis-regulatory regions of these core ER target genes are poorly conserved suggests that different evolutionary mechanisms are operative at transcriptional control elements than at coding regions. These results predict that certain biological effects of estrogen signaling will differ between mouse and human to a larger extent than previously thought.
         datePublished:2004-08-12T00:00:00Z
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            Direct Target Gene
            Estrogen Receptor Function
            Animal Genetics and Genomics
            Human Genetics
            Plant Genetics and Genomics
            Microbial Genetics and Genomics
            Bioinformatics
            Evolutionary Biology
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      headline:Discovery of estrogen receptor α target genes and response elements in breast tumor cells
      description:Estrogens and their receptors are important in human development, physiology and disease. In this study, we utilized an integrated genome-wide molecular and computational approach to characterize the interaction between the activated estrogen receptor (ER) and the regulatory elements of candidate target genes. Of around 19,000 genes surveyed in this study, we observed 137 ER-regulated genes in T-47D cells, of which only 89 were direct target genes. Meta-analysis of heterogeneous in vitro and in vivo datasets showed that the expression profiles in T-47D and MCF-7 cells are remarkably similar and overlap with genes differentially expressed between ER-positive and ER-negative tumors. Computational analysis revealed a significant enrichment of putative estrogen response elements (EREs) in the cis-regulatory regions of direct target genes. Chromatin immunoprecipitation confirmed ligand-dependent ER binding at the computationally predicted EREs in our highest ranked ER direct target genes, NRIP1, GREB1 and ABCA3. Wider examination of the cis-regulatory regions flanking the transcriptional start sites showed species conservation in mouse-human comparisons in only 6% of predicted EREs. Only a small core set of human genes, validated across experimental systems and closely associated with ER status in breast tumors, appear to be sufficient to induce ER effects in breast cancer cells. That cis-regulatory regions of these core ER target genes are poorly conserved suggests that different evolutionary mechanisms are operative at transcriptional control elements than at coding regions. These results predict that certain biological effects of estrogen signaling will differ between mouse and human to a larger extent than previously thought.
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         Additional Data File
         Putative Target Gene
         Direct Target Gene
         Estrogen Receptor Function
         Animal Genetics and Genomics
         Human Genetics
         Plant Genetics and Genomics
         Microbial Genetics and Genomics
         Bioinformatics
         Evolutionary Biology
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            type:Organization
      name:Vladimir B Bajic
      affiliation:
            name:Institute for Infocomm Research
            address:
               name:Knowledge Extraction Lab, Institute for Infocomm Research, Singapore
               type:PostalAddress
            type:Organization
      name:Lance D Miller
      affiliation:
            name:Genome Institute of Singapore
            address:
               name:Genome Institute of Singapore, Singapore
               type:PostalAddress
            type:Organization
      name:Jan-Åke Gustafsson
      affiliation:
            name:Karolinska Institute
            address:
               name:Center for Biotechnology, Karolinska Institute, Huddinge, Sweden
               type:PostalAddress
            type:Organization
            name:Karolinska Institute
            address:
               name:Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden
               type:PostalAddress
            type:Organization
      name:Edison T Liu
      affiliation:
            name:Genome Institute of Singapore
            address:
               name:Genome Institute of Singapore, Singapore
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Genome Institute of Singapore, Singapore
      name:Center for Biotechnology, Karolinska Institute, Huddinge, Sweden
      name:Genome Institute of Singapore, Singapore
      name:Genome Institute of Singapore, Singapore
      name:Genome Institute of Singapore, Singapore
      name:Center for Biotechnology, Karolinska Institute, Huddinge, Sweden
      name:Genome Institute of Singapore, Singapore
      name:Genome Institute of Singapore, Singapore
      name:Genome Institute of Singapore, Singapore
      name:Genome Institute of Singapore, Singapore
      name:Genome Institute of Singapore, Singapore
      name:Knowledge Extraction Lab, Institute for Infocomm Research, Singapore
      name:Knowledge Extraction Lab, Institute for Infocomm Research, Singapore
      name:Knowledge Extraction Lab, Institute for Infocomm Research, Singapore
      name:Genome Institute of Singapore, Singapore
      name:Center for Biotechnology, Karolinska Institute, Huddinge, Sweden
      name:Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden
      name:Genome Institute of Singapore, Singapore

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