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  • 1
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    Control of pancreas and liver gene expression by HNF transcription factors (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-02-28
    Description: The transcriptional regulatory networks that specify and maintain human tissue diversity are largely uncharted. To gain insight into this circuitry, we used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II, in human liver and pancreatic islets. We identified tissue-specific regulatory circuits formed by HNF1alpha, HNF4alpha, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. Our results suggest how misregulation of HNF4alpha can contribute to type 2 diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012624/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Odom, Duncan T -- Zizlsperger, Nora -- Gordon, D Benjamin -- Bell, George W -- Rinaldi, Nicola J -- Murray, Heather L -- Volkert, Tom L -- Schreiber, Jorg -- Rolfe, P Alexander -- Gifford, David K -- Fraenkel, Ernest -- Bell, Graeme I -- Young, Richard A -- N01-DK-9-2310/DK/NIDDK NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- R01 HG002668-01/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 27;303(5662):1378-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14988562" target="_blank"〉PubMed〈/a〉
    Keywords: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Carbohydrate Metabolism ; *DNA-Binding Proteins ; Diabetes Mellitus, Type 2/etiology/genetics ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome, Human ; Gluconeogenesis ; Hepatocyte Nuclear Factor 1 ; Hepatocyte Nuclear Factor 1-alpha ; Hepatocyte Nuclear Factor 1-beta ; Hepatocyte Nuclear Factor 4 ; Hepatocyte Nuclear Factor 6 ; Hepatocytes/*metabolism ; Homeodomain Proteins/*metabolism ; Humans ; Islets of Langerhans/*metabolism ; Lipid Metabolism ; *Nuclear Proteins ; Oligonucleotide Array Sequence Analysis ; Phosphoproteins/*metabolism ; Precipitin Tests ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; Trans-Activators/*metabolism ; Transcription Factors/*metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-01-22
    Description: Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers. The full repertoire of cyclin D1 functions in normal development and oncogenesis is unclear at present. Here we developed Flag- and haemagglutinin-tagged cyclin D1 knock-in mouse strains that allowed a high-throughput mass spectrometry approach to search for cyclin D1-binding proteins in different mouse organs. In addition to cell cycle partners, we observed several proteins involved in transcription. Genome-wide location analyses (chromatin immunoprecipitation coupled to DNA microarray; ChIP-chip) showed that during mouse development cyclin D1 occupies promoters of abundantly expressed genes. In particular, we found that in developing mouse retinas-an organ that critically requires cyclin D1 function-cyclin D1 binds the upstream regulatory region of the Notch1 gene, where it serves to recruit CREB binding protein (CBP) histone acetyltransferase. Genetic ablation of cyclin D1 resulted in decreased CBP recruitment, decreased histone acetylation of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclin D1-null (Ccnd1(-/-)) retinas. Transduction of an activated allele of Notch1 into Ccnd1(-/-) retinas increased proliferation of retinal progenitor cells, indicating that upregulation of Notch1 signalling alleviates the phenotype of cyclin D1-deficiency. These studies show that in addition to its well-established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development. Our approach, which we term 'genetic-proteomic', can be used to study the in vivo function of essentially any protein.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943587/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943587/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bienvenu, Frederic -- Jirawatnotai, Siwanon -- Elias, Joshua E -- Meyer, Clifford A -- Mizeracka, Karolina -- Marson, Alexander -- Frampton, Garrett M -- Cole, Megan F -- Odom, Duncan T -- Odajima, Junko -- Geng, Yan -- Zagozdzon, Agnieszka -- Jecrois, Marie -- Young, Richard A -- Liu, X Shirley -- Cepko, Constance L -- Gygi, Steven P -- Sicinski, Piotr -- 15603/Cancer Research UK/United Kingdom -- A15603/Cancer Research UK/United Kingdom -- HG004069/HG/NHGRI NIH HHS/ -- HG3456/HG/NHGRI NIH HHS/ -- P01 CA080111/CA/NCI NIH HHS/ -- P01 CA080111-128270/CA/NCI NIH HHS/ -- P01 CA109901/CA/NCI NIH HHS/ -- P01 CA109901-067138/CA/NCI NIH HHS/ -- P01 CA109901-067140/CA/NCI NIH HHS/ -- R01 CA108420/CA/NCI NIH HHS/ -- R01 CA108420-07/CA/NCI NIH HHS/ -- R01 EY008064/EY/NEI NIH HHS/ -- R01 EY009676/EY/NEI NIH HHS/ -- R01 EY009676-18/EY/NEI NIH HHS/ -- R01 EYO9676/PHS HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- R01 HG002668-07/HG/NHGRI NIH HHS/ -- R01 HG003456/HG/NHGRI NIH HHS/ -- R01 HG003456-06/HG/NHGRI NIH HHS/ -- R01 HG004069/HG/NHGRI NIH HHS/ -- R01 HG004069-04/HG/NHGRI NIH HHS/ -- Cancer Research UK/United Kingdom -- England -- Nature. 2010 Jan 21;463(7279):374-8. doi: 10.1038/nature08684.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20090754" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; CREB-Binding Protein/metabolism ; Chromatin Immunoprecipitation ; Cyclin D1/deficiency/genetics/*metabolism ; *Gene Expression Regulation, Developmental ; Genome/genetics ; High-Throughput Screening Assays ; Histone Acetyltransferases/metabolism ; Mass Spectrometry ; Mice ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic/genetics ; Protein Binding ; *Proteomics/methods ; Rats ; Receptor, Notch1/genetics/metabolism ; Retina/cytology/embryology/metabolism ; Stem Cells/cytology/metabolism ; *Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Species-specific transcription in mice carrying human chromosome 21 (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-09-13
    Description: Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor-binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by human genetic sequence or mouse nuclear environment. Virtually all transcription factor-binding locations, landmarks of transcription initiation, and the resulting gene expression observed in human hepatocytes were recapitulated across the entire human chromosome 21 in the mouse hepatocyte nucleus. Thus, in homologous tissues, genetic sequence is largely responsible for directing transcriptional programs; interspecies differences in epigenetic machinery, cellular environment, and transcription factors themselves play secondary roles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717767/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717767/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Michael D -- Barbosa-Morais, Nuno L -- Schmidt, Dominic -- Conboy, Caitlin M -- Vanes, Lesley -- Tybulewicz, Victor L J -- Fisher, Elizabeth M C -- Tavare, Simon -- Odom, Duncan T -- 080174/Wellcome Trust/United Kingdom -- 15603/Cancer Research UK/United Kingdom -- 202218/European Research Council/International -- A15603/Cancer Research UK/United Kingdom -- G0601056/Medical Research Council/United Kingdom -- MC_U117527252/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2008 Oct 17;322(5900):434-8. doi: 10.1126/science.1160930. Epub 2008 Sep 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18787134" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Nucleus/metabolism ; Chromatin Assembly and Disassembly ; Chromatin Immunoprecipitation ; Chromosomes, Human, Pair 21/*genetics/metabolism ; Disease Models, Animal ; Down Syndrome/genetics ; *Gene Expression Regulation ; Hepatocyte Nuclear Factors/*metabolism ; Hepatocytes/*metabolism ; Histones/metabolism ; Humans ; Methylation ; Mice ; Oligonucleotide Array Sequence Analysis ; *Regulatory Sequences, Nucleic Acid ; Species Specificity ; Transcription Initiation Site ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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