Author
Kazuhiko Umesono
Other affiliations: Max Planck Society, Kettering University, Howard Hughes Medical Institute ...read more
Bio: Kazuhiko Umesono is an academic researcher from Kyoto University. The author has contributed to research in topics: Retinoic acid receptor & Retinoid X receptor gamma. The author has an hindex of 48, co-authored 98 publications receiving 23671 citations. Previous affiliations of Kazuhiko Umesono include Max Planck Society & Kettering University.
Papers published on a yearly basis
Papers
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TL;DR: This research presents a new probabilistic procedure called ‘spot-spot analysis’ to characterize the response of the immune system to the presence of E.coli.
6,818 citations
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TL;DR: The coupling of the peroxisome proliferator and retinoid signalling pathways is demonstrated and evidence for a physiological role for 9-cis retinoic acid in modulating lipid metabolism is provided.
Abstract: Peroxisomes are cytoplasmic organelles which are important in mammals in modulation of lipid homeostasis, including the metabolism of long-chain fatty acids and conversion of cholesterol to bile salts (reviewed in refs 1 and 2). Amphipathic carboxylates such as clofibric acid have been used in man as hypolipidaemic agents and in rodents they stimulate the proliferation of peroxisomes. These agents, termed peroxisome proliferators, and all-trans retinoic acid activate genes involved in peroxisomal-mediated beta-oxidation of fatty acids. Here we show that the receptor activated by peroxisome proliferators and the retinoid X receptor-alpha (ref. 6) form a heterodimer that activates acyl-CoA oxidase gene expression in response to either clofibric acid or the retinoid X receptor-alpha ligand, 9-cis retinoic acid, an all-trans retinoic acid metabolite; simultaneous exposure to both activators results in a synergistic induction of gene expression. These data demonstrate the coupling of the peroxisome proliferator and retinoid signalling pathways and provide evidence for a physiological role for 9-cis retinoic acid in modulating lipid metabolism.
1,731 citations
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TL;DR: This study points to the general importance of tandem repeat hormone response elements and suggests a simple physiologic code exists in which half-site spacing plays a critical role in achieving selective hormonal response.
1,660 citations
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TL;DR: It is reported that the transcriptional activity of RAR and RXR can be reciprocally modulated by direct interactions between the two proteins, indicating that RXR has a central role in multiple hormonal signalling pathways.
Abstract: CELLULAR responsiveness to retinoic acid and its metabolites is conferred through two structurally and pharmacologically distinct1 families of receptors: the retinoic acid receptors (RAR)2,3 and the retinoid X receptors (RXR)1. Here we report that the transcriptional activity of RAR and RXR can be reciprocally modulated by direct interactions between the two proteins. RAR and RXR have a high degree of cooperativity in binding to target DNA, consistent with previous reports indicating that the binding of either RAR or RXR to their cognate response elements is enhanced by factors present in nuclear extracts4,5. RXR also interacts directly with and enhances the binding of nuclear receptors conferring responsiveness to vitamin D3 and thyroid hormone T3; the DNA-binding activities of these receptors are also stimulated by the presence of nuclear extracts6–9. Together these data indicate that RXR has a central role in multiple hormonal signalling pathways.
1,468 citations
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TL;DR: The complete sequence of the chloroplast DNA from a liverwort, Marchantia polymorpha, is determined and the gene organization is deduced, including coding sequences for four kinds of ribosomal RNAs, 32 species of transfer RNAs and 55 identified open reading frames for proteins, which are separated by short A+T-rich spacers.
Abstract: Chloroplasts contain their own autonomously replicating DNA genome. The majority of proteins present in the chloroplasts are encoded by nuclear DNA, but the rest are encoded by chloroplast DNA and synthesized by the chloroplast transcription–translation machinery1–4. Although the nucleotide sequences of many chloroplast genes from various plant species have been determined, the entire gene organization of the chloroplast genome has not yet been elucidated for any species of plants. To improve our understanding of the chloroplast gene system, we have determined the complete sequence of the chloroplast DNA from a liverwort, Marchantia polymorpha, and deduced the gene organization. As reported here the liverwort chloroplast DNA contains 121,024 base pairs (bp), consisting of a set of large inverted repeats (IRA and IRB, each of 10,058 bp) separated by a small single-copy region (SSC, 19,813 bp) and a large single-copy region (LSC, 81,095 bp). We detected 128 possible genes throughout the liverwort chloroplast genome, including coding sequences for four kinds of ribosomal RNAs, 32 species of transfer RNAs and 55 identified open reading frames (ORFs) for proteins, which are separated by short A+T-rich spacers (Fig. 1). Twenty genes (8 encoding tRNAs, 12 encoding proteins) contain introns in their coding sequences. These introns can be classified as belonging to either group I or group II, as described for mitochondria5. Interestingly, seven of the identified ORFs show high homology to unidentified reading frames (URFs) found in human mitochondria6,7.
1,407 citations
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TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
Abstract: Overlapping complementary DNA clones were isolated from epithelial cell libraries with a genomic DNA segment containing a portion of the putative cystic fibrosis (CF) locus, which is on chromosome 7 Transcripts, approximately 6500 nucleotides in size, were detectable in the tissues affected in patients with CF The predicted protein consists of two similar motifs, each with (i) a domain having properties consistent with membrane association and (ii) a domain believed to be involved in ATP (adenosine triphosphate) binding A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients
6,731 citations
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TL;DR: An approach for genome analysis based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence of the genome from the bacterium Haemophilus influenzae Rd.
Abstract: An approach for genome analysis based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830,137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genome maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence DataBase accession number L42023) represents the only complete genome sequence from a free-living organism.
5,944 citations
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TL;DR: Six primers for the amplification of three non-coding regions of chloroplast DNA via the polymerase chain reaction (PCR) have been designed and worked for most species tested, which means that they may be used to study the population biology and evolution of plants.
Abstract: Six primers for the amplification of three non-coding regions of chloroplast DNA via the polymerase chain reaction (PCR) have been designed. In order to find out whether these primers were universal, we used them in an attempt to amplify DNA from various plant species. The primers worked for most species tested including algae, bryophytes, pteridophytes, gymnosperms and angiosperms. The fact that they amplify chloroplast DNA non-coding regions over a wide taxonomic range means that these primers may be used to study the population biology (in supplying markers) and evolution (inter- and probably intraspecific phylogenies) of plants.
5,212 citations
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Massachusetts Institute of Technology1, Broad Institute2, University of California, Los Angeles3, University of British Columbia4, Baylor College of Medicine5, Howard Hughes Medical Institute6, University of Washington7, Ludwig Institute for Cancer Research8, University of California, San Francisco9, University of Connecticut10, University of Zagreb11, University of Texas at Austin12, Washington University in St. Louis13, University of Queensland14, Harvard University15, Cold Spring Harbor Laboratory16, University of Southern California17, University of California, Santa Cruz18, Simon Fraser University19, Morgridge Institute for Research20, University of Texas at Dallas21, National Institutes of Health22
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
5,037 citations
01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
4,409 citations