Preface Biological Significance and Evolution The continuing quest to comprehend genomic imprinti... more Preface Biological Significance and Evolution The continuing quest to comprehend genomic imprinting: Miyoshi, N. Barton, S.C. Kaneda, M. Hajkova, P. Surani, M.A. Imprinting today: end of the beginning or beginning of the end?: Solter, D. Interactions between imprinting effects: summary and review: Cattanach, B.M. Beechey, C.V. Peters, J. Complementation hypothesis: the necessity of a monoallelic gene expression mechanism in mammalian development: Kaneko-Ishino, T. Kohda, T. Ono, R. Ishino, F. Genomic imprinting is a barrier to parthenogenesis in mammals: Kono, T. Origins of extreme sexual dimorphism in genomic imprinting: Bourc'his, D. Bestor, T.H. Regulatory Mechanisms How imprinting centres work: Lewis, A. Reik, W. Genomic imprinting in the placenta: Wagschal, A. Feil, R. Small non-coding RNAs and genomic imprinting: Royo, H. Bortolin, M.-L. Seitz, H. Cavaille, J. Repetitive elements in imprinted genes: Walter, J. Hutter, B. Khare, T. Paulsen, M. The role of DMDs in the maintenance of epigenetic states: Paoloni-Giacobino, A. Chaillet, J.R. Regulation of imprinted DNA methylation: Holmes, R. Soloway, P.D. Imprinted Genes/Domains Genome-wide survey of imprinted genes: Maeda, N. Hayashizaki, Y. Establishment and maintenance of H19 imprinting in the germline and preimplantation embryo: Reese, K.J. Bartolomei, M.S. Lessons from comparative analysis of species-specific imprinted genes: Okamura, K. Ito, T. The imprinted mouse Igf2r/Air cluster - a model maternal imprinting system: Regha, K. Latos, P.A. Spahn, L. Imprinting the Gnas locus: Plagge, A. Kelsey, G. The H19 gene: regulation and function of a non-coding RNA: Gabory, A. Ripoche, M.-A. Yoshimizu, T. Dandolo, L. Imprinting control within the compact Gnas locus: Peters, J. Holmes, R. Monk, D. Beechey, C.V. Moore, G.E. Williamson, C.M. Cross-species clues of an epigenetic imprinting regulatory code for the IGF2R gene: Vu, T.H. Jirtle, R.L. Hoffman, A.R. Imprinting in neurons: Kishino, T. Analysis of mouse conceptuses with uniparental duplication/deficiency for distal chromosome 12: comparison with chromosome 12 uniparental disomy and implications for genomic imprinting: Tevendale, M. Watkins, M. Rasberry, C. Cattanach, B. Ferguson-Smith, A.C. Human Disease Imprinted genes and their role in human fetal growth: Abu-Amero, S. Monk, D. Apostolidou, S. Stanier, P. Moore, G. Imprinted genes in placental growth and obstetric disorders: Tycko, B. Regulation of growth and metabolism by imprinted genes: Smith, F.M. Garfield, A.S. Ward, A. Imprinting defects on human chromosome 15: Horsthemke, B. Buiting, K. The Prader-Willi/Angelman imprinted domain and its control center: Kantor, B. Shemer, R. Razin, A. Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms causing Beckwith-Wiedemann syndrome and cancer: Higashimoto, K. Soejima, H. Saito, T. Okumura, K. Mukai, T. X Chromosome Inactivation The dynamics of imprinted X inactivation during preimplantation development in mice: Okamoto, I. Heard, E. A SAGE approach to identifying novel trans-acting factors involved in the X inactivation process: Bourdet, A. Ciaudo, C. Zakin, L. Elalouf, J.-M. Rusniol, C. Weissenbach, J. Avner, P. Evolution of mammalian X chromosome-linked imprinting: Mills, W. Moore, T. Author Index.
Biochemical and Biophysical Research Communications, Aug 1, 1981
Highly purified penicillin-binding protein 3 of Escherichia coli was shown to synthesize crosslin... more Highly purified penicillin-binding protein 3 of Escherichia coli was shown to synthesize crosslinked peptidoglycan from the lipid-linked precursor, N-acetylglucosaminyl-N-acetylmuramyl(-pentapeptide )-diphosphoryl undecaprenol through two successive enzymatic reactions, glycan chain ...
Phosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival, ... more Phosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival, and tumorigenesis as well as cellular reprogramming including generation of induced pluripotent stem cells (iPSCs). In this study, we revealed that activation of AKT in somatic cells undergoing reprogramming enhances epigenetic reprogramming. Activated AKT in reprogramming cells triggers elevated anabolic glucose metabolism, and, accordingly, increases the level of α-ketoglutarate (αKG) which is an essential cofactor for the enzymatic activity of the 5-methylcytosine (5mC) dioxygenase TET. Additionally, the level of TET was upregulated. Consistent with upregulated αKG production and TET, we observed a genome-wide increase in 5-hydorxymethylcytosine (5hmC) which is an intermediate in the DNA demethylation process. Moreover, DNA methylation level at ES-cell super-enhancers of pluripotency-related genes was significantly decreased, leading upregulation of associated genes. Taken together, our results indicate that AKT signaling is associated with epigenetic regulation by hyperactivating TET at catalytical and transcriptional levels during the somatic cell reprogramming.
<p>(A) Exon-intron structure of the <i>Sirh11/Zcchc16</i> gene. The full-length... more <p>(A) Exon-intron structure of the <i>Sirh11/Zcchc16</i> gene. The full-length cDNA sequence was identified by 5'- and 3'-RACE (Rapid Amplification of cDNA Ends) experiments using brain RNA at 8 w. The <i>Sirh11/Zcchc16</i> gene consists of 7 exons and the protein coding sequence is in exon 7. The identified cDNA sequence corresponds to Genbank Accession No. NM_001033795.4. The white and black boxes represent the exons and ORF, respectively. (B) <i>Sirh11</i> expression in fetuses and adults. qRT-PCR analyses were carried out using C57BL/6J cDNA from various tissues and organs at d14.5 and 8 w. The black and white bars indicate males and females, respectively. Data represents the mean ± S. D. (N = 3 each). <i>Sirh11/Zcchc16</i> expression was observed in the brain, testis, ovary and kidney, but not in the placenta. qRT-PCR primers (F9R9) were designed in the 3’ UTR region of <i>Sirh11/Zcchc16</i> mRNA (see arrows in Fig 2A). (C) Overexpression of the <i>Sirh11/Zcchc16</i> transcript without any ORF in KO mice. The graph shows the <i>Sirh11/Zcchc16</i> expression levels at 8 weeks of age using F9R9 (3’ UTR) primer sets relative to <i>Actb</i> mRNA in the male brain, kidney and testis. The white and black bars represent WT and KO, respectively. Each data point represents the mean ± S. D. (N = 4 each). The asterisks indicate significant differences between the WT and KO mice (**: p < 0.01).</p
MT-141, a new cephamycin (7 alpha-methoxy-cephalosporin) antibiotic with a D-cysteine moiety in i... more MT-141, a new cephamycin (7 alpha-methoxy-cephalosporin) antibiotic with a D-cysteine moiety in its 7 beta-side chain, has binding affinities to penicillin-binding proteins of Escherichia coli and an inhibitory action on their transpeptidase activity similar to those of other structurally related cephamycins. Yet this antibiotic was found to exert an exceedingly strong and rapid lytic action on sensitive Gram-negative bacteria such as E. coli, Klebsiella pneumoniae, Serratia marcescens and Salmonella enteritidis. Not only rapidly growing cells, but also slowly growing dense cells of the above bacteria could be lysed by this antibiotic at low concentrations. In the presence of 20% sucrose, low concentrations of MT-141 induced smooth-surfaced single and twin bulges of the putative growth zone of the cells and irregularly orientated rough-surfaced bulges. Probably the 7 beta-side chain structure of this antibiotic is involved in its rapid and strong bacteriolytic action.
The localization of the active site of penicillin-binding protein 5 from the dacA mutant of Esche... more The localization of the active site of penicillin-binding protein 5 from the dacA mutant of Escherichia coli strain TMRL 1222 has been determined. The protein was purified to homogeneity and labeled with [14C] penicillin G. The labeled protein was digested with trypsin, and the active site tryptic peptide was purified by a combination of gel filtration and high-pressure liquid chromatography. Sequencing of the purified [14C]penicilloyl peptide yielded the sequence Arg-Asp-Pro-Ala-Ser-Leu-Thr-Lys, which corresponds to residues 40-47 of the gene sequence (Broome-Smith, J., Edelman, A., and Spratt, B. G. (1983) in The Target of Penicillin (Hakenbeck, R., Holtje, J.-V., and Labischinski, H., eds) pp. 403-408, Walter de Gruyter, Berlin). The catalytic amino acid residue that forms a covalent bond with penicillin was identified by treating the purified [14C]penicilloyl peptide with a mixture of proteases and then separating the radioactive products using high-pressure liquid chromatography. Analysis of the radioactive peaks by amino acid analysis confirmed that it is the serine residue that reacts with the beta-lactam ring of penicillin.
ObjectiveAlthough immunoglobulin A (IgA) is abundantly expressed in the gut and known to be an im... more ObjectiveAlthough immunoglobulin A (IgA) is abundantly expressed in the gut and known to be an important component of mucosal barriers against luminal pathogens, its precise function remains unclear. Therefore, we tried to elucidate the effect of IgA on gut homeostasis maintenance and its mechanism.DesignWe generated various IgA mutant mouse lines using the CRISPR/Cas9 genome editing system. Then, we evaluated the effect on the small intestinal homeostasis, pathology, intestinal microbiota, cytokine production, and immune cell activation using intravital imaging.ResultsWe obtained two lines, with one that contained a <50 base pair deletion in the cytoplasmic region of the IgA allele (IgA tail-mutant; IgAtm/tm) and the other that lacked the most constant region of the IgH α chain, which resulted in the deficiency of IgA production (IgA−/−). IgA−/− exhibited spontaneous inflammation in the ileum but not the other parts of the gastrointestinal tract. Associated with this, there were significantly increased lamina propria CD4+T cells, elevated productions of IFN-γ and IL-17, increased ileal segmented filamentous bacteria and skewed intestinal microflora composition. Intravital imaging using Ca2+ biosensor showed that IgA−/− had elevated Ca2+ signalling in Peyer’s patch B cells. On the other hand, IgAtm/tm seemed to be normal, suggesting that the IgA cytoplasmic tail is dispensable for the prevention of the intestinal disorder.ConclusionIgA plays an important role in the mucosal homeostasis associated with the regulation of intestinal microbiota and protection against mucosal inflammation especially in the ileum.
Preface Biological Significance and Evolution The continuing quest to comprehend genomic imprinti... more Preface Biological Significance and Evolution The continuing quest to comprehend genomic imprinting: Miyoshi, N. Barton, S.C. Kaneda, M. Hajkova, P. Surani, M.A. Imprinting today: end of the beginning or beginning of the end?: Solter, D. Interactions between imprinting effects: summary and review: Cattanach, B.M. Beechey, C.V. Peters, J. Complementation hypothesis: the necessity of a monoallelic gene expression mechanism in mammalian development: Kaneko-Ishino, T. Kohda, T. Ono, R. Ishino, F. Genomic imprinting is a barrier to parthenogenesis in mammals: Kono, T. Origins of extreme sexual dimorphism in genomic imprinting: Bourc'his, D. Bestor, T.H. Regulatory Mechanisms How imprinting centres work: Lewis, A. Reik, W. Genomic imprinting in the placenta: Wagschal, A. Feil, R. Small non-coding RNAs and genomic imprinting: Royo, H. Bortolin, M.-L. Seitz, H. Cavaille, J. Repetitive elements in imprinted genes: Walter, J. Hutter, B. Khare, T. Paulsen, M. The role of DMDs in the maintenance of epigenetic states: Paoloni-Giacobino, A. Chaillet, J.R. Regulation of imprinted DNA methylation: Holmes, R. Soloway, P.D. Imprinted Genes/Domains Genome-wide survey of imprinted genes: Maeda, N. Hayashizaki, Y. Establishment and maintenance of H19 imprinting in the germline and preimplantation embryo: Reese, K.J. Bartolomei, M.S. Lessons from comparative analysis of species-specific imprinted genes: Okamura, K. Ito, T. The imprinted mouse Igf2r/Air cluster - a model maternal imprinting system: Regha, K. Latos, P.A. Spahn, L. Imprinting the Gnas locus: Plagge, A. Kelsey, G. The H19 gene: regulation and function of a non-coding RNA: Gabory, A. Ripoche, M.-A. Yoshimizu, T. Dandolo, L. Imprinting control within the compact Gnas locus: Peters, J. Holmes, R. Monk, D. Beechey, C.V. Moore, G.E. Williamson, C.M. Cross-species clues of an epigenetic imprinting regulatory code for the IGF2R gene: Vu, T.H. Jirtle, R.L. Hoffman, A.R. Imprinting in neurons: Kishino, T. Analysis of mouse conceptuses with uniparental duplication/deficiency for distal chromosome 12: comparison with chromosome 12 uniparental disomy and implications for genomic imprinting: Tevendale, M. Watkins, M. Rasberry, C. Cattanach, B. Ferguson-Smith, A.C. Human Disease Imprinted genes and their role in human fetal growth: Abu-Amero, S. Monk, D. Apostolidou, S. Stanier, P. Moore, G. Imprinted genes in placental growth and obstetric disorders: Tycko, B. Regulation of growth and metabolism by imprinted genes: Smith, F.M. Garfield, A.S. Ward, A. Imprinting defects on human chromosome 15: Horsthemke, B. Buiting, K. The Prader-Willi/Angelman imprinted domain and its control center: Kantor, B. Shemer, R. Razin, A. Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms causing Beckwith-Wiedemann syndrome and cancer: Higashimoto, K. Soejima, H. Saito, T. Okumura, K. Mukai, T. X Chromosome Inactivation The dynamics of imprinted X inactivation during preimplantation development in mice: Okamoto, I. Heard, E. A SAGE approach to identifying novel trans-acting factors involved in the X inactivation process: Bourdet, A. Ciaudo, C. Zakin, L. Elalouf, J.-M. Rusniol, C. Weissenbach, J. Avner, P. Evolution of mammalian X chromosome-linked imprinting: Mills, W. Moore, T. Author Index.
Biochemical and Biophysical Research Communications, Aug 1, 1981
Highly purified penicillin-binding protein 3 of Escherichia coli was shown to synthesize crosslin... more Highly purified penicillin-binding protein 3 of Escherichia coli was shown to synthesize crosslinked peptidoglycan from the lipid-linked precursor, N-acetylglucosaminyl-N-acetylmuramyl(-pentapeptide )-diphosphoryl undecaprenol through two successive enzymatic reactions, glycan chain ...
Phosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival, ... more Phosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival, and tumorigenesis as well as cellular reprogramming including generation of induced pluripotent stem cells (iPSCs). In this study, we revealed that activation of AKT in somatic cells undergoing reprogramming enhances epigenetic reprogramming. Activated AKT in reprogramming cells triggers elevated anabolic glucose metabolism, and, accordingly, increases the level of α-ketoglutarate (αKG) which is an essential cofactor for the enzymatic activity of the 5-methylcytosine (5mC) dioxygenase TET. Additionally, the level of TET was upregulated. Consistent with upregulated αKG production and TET, we observed a genome-wide increase in 5-hydorxymethylcytosine (5hmC) which is an intermediate in the DNA demethylation process. Moreover, DNA methylation level at ES-cell super-enhancers of pluripotency-related genes was significantly decreased, leading upregulation of associated genes. Taken together, our results indicate that AKT signaling is associated with epigenetic regulation by hyperactivating TET at catalytical and transcriptional levels during the somatic cell reprogramming.
<p>(A) Exon-intron structure of the <i>Sirh11/Zcchc16</i> gene. The full-length... more <p>(A) Exon-intron structure of the <i>Sirh11/Zcchc16</i> gene. The full-length cDNA sequence was identified by 5'- and 3'-RACE (Rapid Amplification of cDNA Ends) experiments using brain RNA at 8 w. The <i>Sirh11/Zcchc16</i> gene consists of 7 exons and the protein coding sequence is in exon 7. The identified cDNA sequence corresponds to Genbank Accession No. NM_001033795.4. The white and black boxes represent the exons and ORF, respectively. (B) <i>Sirh11</i> expression in fetuses and adults. qRT-PCR analyses were carried out using C57BL/6J cDNA from various tissues and organs at d14.5 and 8 w. The black and white bars indicate males and females, respectively. Data represents the mean ± S. D. (N = 3 each). <i>Sirh11/Zcchc16</i> expression was observed in the brain, testis, ovary and kidney, but not in the placenta. qRT-PCR primers (F9R9) were designed in the 3’ UTR region of <i>Sirh11/Zcchc16</i> mRNA (see arrows in Fig 2A). (C) Overexpression of the <i>Sirh11/Zcchc16</i> transcript without any ORF in KO mice. The graph shows the <i>Sirh11/Zcchc16</i> expression levels at 8 weeks of age using F9R9 (3’ UTR) primer sets relative to <i>Actb</i> mRNA in the male brain, kidney and testis. The white and black bars represent WT and KO, respectively. Each data point represents the mean ± S. D. (N = 4 each). The asterisks indicate significant differences between the WT and KO mice (**: p < 0.01).</p
MT-141, a new cephamycin (7 alpha-methoxy-cephalosporin) antibiotic with a D-cysteine moiety in i... more MT-141, a new cephamycin (7 alpha-methoxy-cephalosporin) antibiotic with a D-cysteine moiety in its 7 beta-side chain, has binding affinities to penicillin-binding proteins of Escherichia coli and an inhibitory action on their transpeptidase activity similar to those of other structurally related cephamycins. Yet this antibiotic was found to exert an exceedingly strong and rapid lytic action on sensitive Gram-negative bacteria such as E. coli, Klebsiella pneumoniae, Serratia marcescens and Salmonella enteritidis. Not only rapidly growing cells, but also slowly growing dense cells of the above bacteria could be lysed by this antibiotic at low concentrations. In the presence of 20% sucrose, low concentrations of MT-141 induced smooth-surfaced single and twin bulges of the putative growth zone of the cells and irregularly orientated rough-surfaced bulges. Probably the 7 beta-side chain structure of this antibiotic is involved in its rapid and strong bacteriolytic action.
The localization of the active site of penicillin-binding protein 5 from the dacA mutant of Esche... more The localization of the active site of penicillin-binding protein 5 from the dacA mutant of Escherichia coli strain TMRL 1222 has been determined. The protein was purified to homogeneity and labeled with [14C] penicillin G. The labeled protein was digested with trypsin, and the active site tryptic peptide was purified by a combination of gel filtration and high-pressure liquid chromatography. Sequencing of the purified [14C]penicilloyl peptide yielded the sequence Arg-Asp-Pro-Ala-Ser-Leu-Thr-Lys, which corresponds to residues 40-47 of the gene sequence (Broome-Smith, J., Edelman, A., and Spratt, B. G. (1983) in The Target of Penicillin (Hakenbeck, R., Holtje, J.-V., and Labischinski, H., eds) pp. 403-408, Walter de Gruyter, Berlin). The catalytic amino acid residue that forms a covalent bond with penicillin was identified by treating the purified [14C]penicilloyl peptide with a mixture of proteases and then separating the radioactive products using high-pressure liquid chromatography. Analysis of the radioactive peaks by amino acid analysis confirmed that it is the serine residue that reacts with the beta-lactam ring of penicillin.
ObjectiveAlthough immunoglobulin A (IgA) is abundantly expressed in the gut and known to be an im... more ObjectiveAlthough immunoglobulin A (IgA) is abundantly expressed in the gut and known to be an important component of mucosal barriers against luminal pathogens, its precise function remains unclear. Therefore, we tried to elucidate the effect of IgA on gut homeostasis maintenance and its mechanism.DesignWe generated various IgA mutant mouse lines using the CRISPR/Cas9 genome editing system. Then, we evaluated the effect on the small intestinal homeostasis, pathology, intestinal microbiota, cytokine production, and immune cell activation using intravital imaging.ResultsWe obtained two lines, with one that contained a <50 base pair deletion in the cytoplasmic region of the IgA allele (IgA tail-mutant; IgAtm/tm) and the other that lacked the most constant region of the IgH α chain, which resulted in the deficiency of IgA production (IgA−/−). IgA−/− exhibited spontaneous inflammation in the ileum but not the other parts of the gastrointestinal tract. Associated with this, there were significantly increased lamina propria CD4+T cells, elevated productions of IFN-γ and IL-17, increased ileal segmented filamentous bacteria and skewed intestinal microflora composition. Intravital imaging using Ca2+ biosensor showed that IgA−/− had elevated Ca2+ signalling in Peyer’s patch B cells. On the other hand, IgAtm/tm seemed to be normal, suggesting that the IgA cytoplasmic tail is dispensable for the prevention of the intestinal disorder.ConclusionIgA plays an important role in the mucosal homeostasis associated with the regulation of intestinal microbiota and protection against mucosal inflammation especially in the ileum.
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Papers by Fumitoshi Ishino