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T Murata,
K Takayama,
S Katayama,
T Urano,
K Horie-Inoue,
K Ikeda,
S Takahashi,
C Kawazu,
A Hasegawa,
Y Ouchi,
Y Homma, Y Hayashizaki,
S Inoue
[show abstract]
[hide abstract]
ABSTRACT: Recent advances in cancer biology reveal that microRNAs (miRNAs) are involved in the regulation of cancer-related genes, or they function as tumor suppressors or oncogenes. In prostate cancer, evidence has accumulated for the contribution of the androgen-dependent gene network to tumor growth, although the precise functions of miRNAs in prostate cancer remain to be investigated. Here, we identified androgen-responsive miRNAs by the short RNA sequencing analysis in LNCaP prostate cancer cells. Among 10 miRNAs with known sequences, we have determined that miR-148a reduces the expression of cullin-associated and neddylation-dissociated 1 (CAND1), a negative regulator of SKP1-Cullin1-F-box (SCF) ubiquitin ligases, by binding to the 3'-untranslated region of CAND1 mRNA. CAND1 knockdown by small interfering RNA promoted the proliferation of LNCaP cells. Our study indicates the potential contribution of miR-148a to the growth of human prostate cancer.
Prostate cancer and prostatic diseases 12/2010; 13(4):356-61. · 2.10 Impact Factor
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K Takayama,
S Tsutsumi,
S Katayama,
T Okayama,
K Horie-Inoue,
K Ikeda,
T Urano,
C Kawazu,
A Hasegawa,
K Ikeo,
T Gojyobori,
Y Ouchi, Y Hayashizaki,
H Aburatani,
S Inoue
[show abstract]
[hide abstract]
ABSTRACT: The androgen receptor (AR) is a critical transcriptional factor that contributes to the development and the progression of prostate cancer (PCa) by regulating the transcription of various target genes. Genome-wide screening of androgen target genes provides useful information to understand a global view of AR-mediated gene network in PCa. In this study, we performed 5'-cap analysis of gene expression (CAGE) to determine androgen-regulated transcription start sites (TSSs) and chromatin immunoprecipitation (ChIP) on array (ChIP-chip) analysis to identify AR binding sites (ARBSs) and histone H3 acetylated (AcH3) sites in the human genome. CAGE determined 13 110 distinct, androgen-regulated TSSs (P<0.01), and ChIP-chip analysis identified 2872 androgen-dependent ARBSs (P<1e-5) and 25 945 AcH3 sites (P<1e-4). Both androgen-regulated coding genes and noncoding RNAs, including microRNAs (miRNAs) were determined as androgen target genes. Besides prototypic androgen-regulated TSSs in annotated gene promoter regions, there are many androgen-dependent TSSs that are widely distributed throughout the genome, including those in antisense (AS) direction of RefSeq genes. Several pairs of sense/antisense promoters were newly identified within single RefSeq gene regions. The integration of CAGE and ChIP-chip analyses successfully identified a cluster of androgen-inducible miRNAs, as exemplified by the miR-125b-2 cluster on chromosome 21. Notably, the number of androgen-upregulated genes was larger in LNCaP cells treated with R1881 for 24 h than for 6 h, and the percentage of androgen-upregulated genes accompanied with adjacent ARBSs was also much higher in cells treated with R1881 for 24 h than 6 h. On the basis of the Oncomine database, the majority of androgen-upregulated genes containing adjacent ARBSs and CAGE tag clusters in our study were previously confirmed as androgen target genes in PCa. The integrated high-throughput genome analyses of CAGE and ChIP-chip provide useful information for elucidating the AR-mediated transcriptional network that contributes to the development and progression of PCa.
Oncogene 10/2010; 30(5):619-30. · 6.37 Impact Factor
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A R R Forrest,
M Kanamori-Katayama,
Y Tomaru,
T Lassmann,
N Ninomiya,
Y Takahashi,
M J L de Hoon,
A Kubosaki,
A Kaiho,
M Suzuki,
J Yasuda,
J Kawai, Y Hayashizaki,
D A Hume,
H Suzuki
[show abstract]
[hide abstract]
ABSTRACT: Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced microRNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these pro-differentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2009; 24(2):460-6. · 8.30 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: By ablating solid C60 with a laser pulse, we observe various processes such as the prompt- and the delayed-ionization of C60, the fragmentation into molecular ions and the formation of cluster ions. We found these processes show distinct dependences
on the temporal pulse width, the power and the wavelength of the ablation laser. From the observations, we could confirm efficient
coupling of laser energy to C60 through the molecular absorption even with a laser pulse width less than the electron-phonon coupling time of the C60 molecule.
Applied Physics A 08/2008; 92(4):777-780. · 1.63 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Time development of Sm+ and Sm ablation plume produced by the femtosecond laser irradiation has been investigated. The two-dimensional spatial profiles
of Sm and Sm+ emitted from oxidized and non-oxidized Sm surface were visualized using a planar laser-induced fluorescence method. It was
observed that the flow velocity of Sm+ is much faster than that of Sm plume in both surfaces. The plumes from the oxidized Sm surface show higher velocity than
that from non-oxidized surface, which is originated by the small electric conductivity at the surface. Expansion property
observed for Sm+ and Sm plume in the oxidized Sm surface ablation implies the formation of the Knundsen layer nearby the surface. Meanwhile,
continuous emission of Sm indicates the large contribution of heating effect to emission process at the non-oxidized surface.
We conclude that the fsLA process strongly depends on the electric property of the ablated surface and the heating effect
contributes to the particle emission process on the conductive material surface.
Applied Physics A 08/2008; 92(4):1047-1050. · 1.63 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: We report here the resonance effect in femtosecond laser ablation of solid C60 by investigating wavelength and fluence dependence of product ion species. When the ablation laser wavelength is far from the molecular absorption band of C60, we observe both C60-2n+ fragment ions and C60+2n+ cluster ions as well as C60+ parent ion. Delayed ionization of C60 is not significant. When the ablation laser wavelength is near resonant with the molecular absorption, we observe C60+ and some amount of C60-2n+ fragment ions depending on the laser fluence. Delayed ionization of C60 is significant in this case, which indicates high internal energy of C60 molecule. From the observations, we confirm the strong coupling of femtosecond laser energy with C60 molecule when the molecular absorption is high at the ablation laser wavelength.
The Journal of Chemical Physics 10/2007; 127(11):111101. · 3.33 Impact Factor
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T. Kobayashi,
T. Kato,
Y. Matsuo,
M. Kurata-Nishimura, Y. Hayashizaki,
J. Kawai,
RIKEN Genomic Science Center, Suehiro-cho, Tsurumi, Yokohama, Kanagawa,
RIKEN Nishina Center for Accelerator-Based Science, Hirosawa, Wako, Saitama
[show abstract]
[hide abstract]
ABSTRACT: We report here the resonance effect in femtosecond laser ablation of solid C{sub 60} by investigating wavelength and fluence dependence of product ion species. When the ablation laser wavelength is far from the molecular absorption band of C{sub 60}, we observe both C{sub 60-2n}{sup +} fragment ions and C{sub 60+2n}{sup +} cluster ions as well as C{sub 60}{sup +} parent ion. Delayed ionization of C{sub 60} is not significant. When the ablation laser wavelength is near resonant with the molecular absorption, we observe C{sub 60}{sup +} and some amount of C{sub 60-2n}{sup +} fragment ions depending on the laser fluence. Delayed ionization of C{sub 60} is significant in this case, which indicates high internal energy of C{sub 60} molecule. From the observations, we confirm the strong coupling of femtosecond laser energy with C{sub 60} molecule when the molecular absorption is high at the ablation laser wavelength.
Journal of Chemical Physics. 09/2007; 127(11).
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[show abstract]
[hide abstract]
ABSTRACT: Ionization and fragmentation of solid C(60) dispersed on a silicon plate are investigated by femtosecond laser ablation. Bimodal mass distribution with large fragment ions C(60-2n) (+) (0< or =n< or =11) and small fragment ions C(n) (+) (13< or =n< or =28), formation of dimer ion (C(60))(2) (+), and delayed ionization of C(60) have been observed as reported in gas phase experiments with nanosecond laser excitation. Metastable dissociation of small fragment ions C(n) (+) has been observed for the first time, which suggests different structures of fragment ions compared with those of well-studied carbon cluster ions. From these observations, strong coupling of laser energy to electronic degrees of freedom of solid C(60) has been revealed for femtosecond laser ablation as compared with excitation in the gas phase.
The Journal of Chemical Physics 02/2007; 126(6):061101. · 3.33 Impact Factor
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S Katayama,
Y Tomaru,
T Kasukawa,
K Waki,
M Nakanishi,
M Nakamura,
H Nishida,
C C Yap,
M Suzuki,
J Kawai, [......],
S Batalov,
P G Engström,
Y Mizuno,
M A Faghihi,
A Sandelin,
A M Chalk,
S Mottagui-Tabar,
Z Liang,
B Lenhard,
C Wahlestedt
[show abstract]
[hide abstract]
ABSTRACT: Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.
Science 10/2005; 309(5740):1564-6. · 31.20 Impact Factor
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P Carninci,
T Kasukawa,
S Katayama,
J Gough,
M C Frith,
N Maeda,
R Oyama,
T Ravasi,
B Lenhard,
C Wells, [......],
K Shibata,
T Shiraki,
S Suzuki,
M Tagami,
K Waki,
A Watahiki,
Y Okamura-Oho,
H Suzuki,
J Kawai, Y Hayashizaki
[show abstract]
[hide abstract]
ABSTRACT: This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
Science 10/2005; 309(5740):1559-63. · 31.20 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: To thoroughly understand the function and regulation of neurotransmitter systems in the brain, as well as the underlying disease mechanisms, it is important to comprehensively analyze the expression patterns of genes participating in such systems. Using functional annotated cDNA clones (FANTOM), we examined the gene expression patterns of the serotonin neurotransmitter system, which is involved in psychiatric diseases such as depression. We chose 24 gene products and visualized their endogenous localizations using in situ hybridization (ISH). We were able to fine-tune an automated ISH method to obtain high-resolution cell-based figures within 24 h. We also measured the amounts of mRNAs with quantitative RT-PCR. The outline of the in situ gene expression pattern viewed under low magnification agreed with the results of the RT-PCR. In the high-resolution view obtained with ISH, we could document novel localizations of the several genes critically related to serotonin activity
Neurobiology of Disease 01/2005; 19(3):378-385. · 5.40 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Recent large-scale genome projects afford a unique opportunity to identify many novel disease genes and thereby better understand the genetic basis of human disease. Functional Annotation of Mouse (FANTOM) 2, the largest mouse transcriptome project yet, provides a wealth of data on novel genes, splice variants and non-coding RNA, and provides a unique opportunity to identify novel human disease genes.
To demonstrate the power of combining the FANTOM 2 cDNA dataset with a positional candidate approach and bioinformatics analysis to identify genes underlying human genetic disease.
By mapping all FANTOM 2 cDNA to the human genome, we were able to identify mouse clones that co-localised on the human genome with mapped but uncloned human disease loci. By this method we identified mouse and corresponding human genes mapping within the loci of 100 different human genetic diseases (mapped interval of <5 cM). Of particular interest was the elucidation through FANTOM 2 novel mouse gene data of candidate human genes for the following: (i) developmental -disorders: neural tube defect, Meckel syndrome, Wolf--Hirschhorn syndrome and keratosis follicularis spinulosa decalvans cum ophiasi; (ii) neurological disorders: benign familial infantile convulsions 3, early-onset cerebellar ataxia with retained tendon reflexes, infantile-onset spinocerebellar ataxia and vacuolar neuro-myopathy and (iii) cancer-related syndromes: tylosis with oesophageal cancer and low-grade B-cell chronic lymphatic leukaemia.
The FANTOM 2 data will dramatically accelerate efforts to identify genes underlying human disease. It will also facilitate the creation of transgenic mouse models to help elucidate the function of potential human disease genes.
Internal Medicine Journal 03/2004; 34(3):79-90. · 1.54 Impact Factor
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E D Jarvis,
V. A. Smith,
K Wada,
M V Rivas,
M. Mcelroy,
T V Smulders,
P Carninci, Y Hayashizaki,
F. Dietrich,
X Wu,
P. Mcconnell,
J Yu,
P. P. Wang,
A. J. Hartemink,
S Lin
[show abstract]
[hide abstract]
ABSTRACT: Biological systems by default involve complex components with complex relationships. To decipher how biological systems work, we assume that one needs to integrate information over multiple levels of complexity. The songbird vocal communication system is ideal for such integration due to many years of ethological investigation and a discreet dedicated brain network. Here we announce the beginnings of a songbird brain integrative project that involves high-throughput, molecular, anatomical, electrophysiological and behavioral levels of analysis. We first formed a rationale for inclusion of specific biological levels of analysis, then developed high-throughput molecular technologies on songbird brains, developed technologies for combined analysis of electrophysiological activity and gene regulation in awake behaving animals, and developed bioinformatic tools that predict causal interactions within and between biological levels of organization. This integrative brain project is fitting for the interdisciplinary approaches taken in the current songbird issue of the Journal of Comparative Physiology A and is expected to be conducive to deciphering how brains generate and perceive complex behaviors.
02/2004;
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Y Ozawa,
S Hanaoka,
R Saito,
T. Washio,
S Nakano,
A Shinagawa,
M Itoh,
K Shibata,
P Carninci,
H Konno,
J Kawai, Y Hayashizaki,
M Tomita
[show abstract]
[hide abstract]
ABSTRACT: Recent investigations into the translation termination sites of various organisms have revealed that not only stop codons but also sequences around stop codons have an effect on translation termination. To investigate the relationship between these sequence patterns and translation as well as its termination efficiency, we analysed the correlation between strength of consensus and translation efficiency, as predicted according to Codon Adaptation Index (CAI) value. We used RIKEN full-length mouse cDNA sequences and ten other eukaryotic UniGene datasets from NCBI for the analyses. First, we conducted sequence profile analyses following translation termination sites. We found base G and A at position as a strong consensus for mouse cDNA. A similar consensus was found for other mammals, such as Homo sapiens, Rattus norvegicus and Bos taurus. However, some plants had different consensus sequences. We then analysed the correlation between the strength of consensus at each position and the codon biases of whole coding regions, using information content and CAI value. The results showed that in mouse cDNA, CAI value had a positive correlation with information content at positions 1.
01/2003;
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E D Jarvis,
V A Smith,
K Wada,
M V Rivas,
M McElroy,
T V Smulders,
P Carninci, Y Hayashizaki,
F Dietrich,
X Wu,
P McConnell,
J Yu,
P P Wang,
A J Hartemink,
S Lin
[show abstract]
[hide abstract]
ABSTRACT: Biological systems by default involve complex components with complex relationships. To decipher how biological systems work, we assume that one needs to integrate information over multiple levels of complexity. The songbird vocal communication system is ideal for such integration due to many years of ethological investigation and a discreet dedicated brain network. Here we announce the beginnings of a songbird brain integrative project that involves high-throughput, molecular, anatomical, electrophysiological and behavioral levels of analysis. We first formed a rationale for inclusion of specific biological levels of analysis, then developed high-throughput molecular technologies on songbird brains, developed technologies for combined analysis of electrophysiological activity and gene regulation in awake behaving animals, and developed bioinformatic tools that predict causal interactions within and between biological levels of organization. This integrative brain project is fitting for the interdisciplinary approaches taken in the current songbird issue of the Journal of Comparative Physiology A and is expected to be conducive to deciphering how brains generate and perceive complex behaviors.
Journal of Comparative Physiology 01/2003; 188(11-12):961-80. · 2.01 Impact Factor
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Y Okazaki,
M Furuno,
T Kasukawa,
J Adachi,
H Bono,
S Kondo,
I Nikaido,
N Osato,
R Saito,
H Suzuki, [......],
D Sasaki,
K Shibata,
A Shinagawa,
A Yasunishi,
M Yoshino,
R Waterston,
E S Lander,
J Rogers,
E Birney, Y Hayashizaki
[show abstract]
[hide abstract]
ABSTRACT: Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
Nature 01/2003; 420(6915):563-73. · 36.28 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: We conducted comprehensive analyses on intron positions in the Mus musculus genome by comparing genomic sequences in the GenBank database and cDNA sequences in the mouse cDNA library recently developed by Riken Genomic Sciences Center. Our results confirm that introns have a tendency to be located toward the 5' end of the gene. The same type of analysis was conducted in the coding region of seven eukaryotes (Saccharomyces cerevisiae, Plasmodium falciparum, Caenorhabditis elegans, Drosophila melanogaster, M. musculus, Homo sapiens, Arabidopsis thaliana). Introns in genes with a single intron have a locational bias toward the 5' end in all species except A. thaliana. We also measured the distance from the start codon to the position of the intron, and found that single introns prefer the location immediately after the start codon in S. cerevisiae and P. falciparum. We discuss three possible explanations for these findings: (1) they are the consequence of intron loss by reverse-transcriptase; (2) they are necessary to accommodate the function; and (3) they are concerned with the mechanism of pre-mRNA splicing.
Gene 11/2002; 300(1-2):89-95. · 2.34 Impact Factor
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Y Ozawa,
S Hanaoka,
R Saito,
T Washio,
S Nakano,
A Shinagawa,
M Itoh,
K Shibata,
P Carninci,
H Konno,
J Kawai, Y Hayashizaki,
M Tomita
[show abstract]
[hide abstract]
ABSTRACT: Recent investigations into the translation termination sites of various organisms have revealed that not only stop codons but also sequences around stop codons have an effect on translation termination. To investigate the relationship between these sequence patterns and translation as well as its termination efficiency, we analysed the correlation between strength of consensus and translation efficiency, as predicted according to Codon Adaptation Index (CAI) value. We used RIKEN full-length mouse cDNA sequences and ten other eukaryotic UniGene datasets from NCBI for the analyses. First, we conducted sequence profile analyses following translation termination sites. We found base G and A at position +1 as a strong consensus for mouse cDNA. A similar consensus was found for other mammals, such as Homo sapiens, Rattus norvegicus and Bos taurus. However, some plants had different consensus sequences. We then analysed the correlation between the strength of consensus at each position and the codon biases of whole coding regions, using information content and CAI value. The results showed that in mouse cDNA, CAI value had a positive correlation with information content at positions +1. We also found that, for positions with strong consensus, the strength of the consensus is likely to have a positive correlation with CAI value in some other eukaryotes. Along with these observations, biological insights into the relationship between gene expression level, codon biases and consensus sequence around stop codons will be discussed.
Gene 11/2002; 300(1-2):79-87. · 2.34 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The quality of collections of expressed sequence tags andfull-length cDNAs is adversely affected by the presence of "junk" clones derivedfrom unspliced or partially spliced RNAs present in conventional total RNA preparations. One can overcome this problem by using intact cytoplasmic RNA to create cDNA libraries, but the methods in the literature that describe the preparation of RNA only work well for extracting cultured cells. Cell lines are not as diverse as one would like, and to clone comprehensive sets of human and model organism full-length cDNAs, libraries have to be prepared from tissue samples. Thus, we have developed a robust and inexpensive method that allows intact cytoplasmic RNA to be extracted from both fresh and frozen mammalian tissues. A mouse full-length, cap-trapped cDNA library prepared with RNA using this new procedure had excellent characteristics.
BioTechniques 09/2002; 33(2):306-9. · 2.67 Impact Factor
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BioTechniques 06/2002; 32(5):984-5. · 2.67 Impact Factor
