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Toxicological study in experimental animal for hazard identification of mycotoxins

Yoshiko SUGITA-KONISHI, Atsutaka KUBOSAKI
2006 JSM Mycotoxins  
Toxicological study in experimental animal for hazard identification of mycotoxins Yoshiko SUGITA-KONISHI and Atsutaka KUBOSAKI: National Institute of Health Sciences (Setagaya, Tokyo 158-8501 Japan  ... 
doi:10.2520/myco.56.105 fatcat:bbtcmsiiibgghambrbpremyume

姿を現わした哺乳動物のRNA新大陸
The Discovery of A Novel RNA Continent

Atsutaka KUBOSAKI, Yoshihide HAYASHIZAKI
2007 KAGAKU TO SEIBUTSU  
doi:10.1271/kagakutoseibutsu1962.45.544 fatcat:23jl5ome2zavvftoc35uf5whyq

Distribution of Sterigmatocystin-producing Aspergilli in Japan

Naoki Kobayashi, Atsutaka Kubosaki, Yumi Takahashi, Miyuki Yanai, Rumi Konuma, Satomi Uehara, Takashi Chiba, Maiko Watanabe, Jun Terajima, Yoshiko Sugita-Konishi
2018 Food Safety  
Sterigmatocystin is a genotoxic and hepatocarcinogenic mycotoxin that contaminates foods and environments worldwide. Sterigmatocystin is produced as a precursor to aflatoxin B1 or as an end product by certain Aspergilli. Aspergillus section Versicolores is one of the major sections including sterigmatocystin-producing species and is thus a potential health and environmental hazard. Recently, the taxonomy of this section was revised and classified into 14 species on the basis of molecular
more » ... netic analysis. However, investigation of the distribution and sterigmatocystin production of each species has been limited; in particular, its distribution in foods has been scarcely reported. In this study, we collected isolates of Aspergillus section Versicolores from various foods and environments in Japan and investigated their distribution and sterigmatocystin production. The isolates were classified into nine species or species groups, which revealed that A. creber, A. puulaauensis/tennesseensis and A. sydowii are the main species/species groups in Japan. In addition, A. versicolor sensu stricto was detected with some frequency, specifically in foods. Furthermore, the two species A. creber and A. versicolor sensu stricto frequently produced sterigmatocystin. It is therefore important for food safety to intensively monitor these two species and distinguish them from other species, especially A. sydowii, which is not considered to produce sterigmatocystin.
doi:10.14252/foodsafetyfscj.2018001 pmid:32231949 pmcid:PMC6989199 fatcat:gt2bd3zf45djpolnyn2raee7sq

Regulatory interdependence of myeloid transcription factors revealed by Matrix RNAi analysis

Yasuhiro Tomaru, Christophe Simon, Alistair RR Forrest, Hisashi Miura, Atsutaka Kubosaki, Yoshihide Hayashizaki, Masanori Suzuki
2009 Genome Biology  
With the move towards systems biology, we need sensitive and reliable ways to determine the relationships between transcription factors and their target genes. In this paper we analyze the regulatory relationships between 78 myeloid transcription factors and their coding genes by using the matrix RNAi system in which a set of transcription factor genes are individually knocked down and the resultant expression perturbation is quantified. Results: Using small interfering RNAs we knocked down the
more » ... 78 transcription factor genes in monocytic THP-1 cells and monitored the perturbation of the expression of the same 78 transcription factors and 13 other transcription factor genes as well as 5 non-transcription factor genes by quantitative real-time RT-PCR, thereby building a 78 × 96 matrix of perturbation and measurement. This approach identified 876 cases where knockdown of one transcription factor significantly affected the expression of another (from a potential 7,488 combinations). Our study also revealed cell-type-specific transcriptional regulatory networks in two different cell types. Conclusions: By considering whether the targets of a given transcription factor are naturally upor downregulated during phorbol 12-myristate 13-acetate-induced differentiation, we could classify these edges as pro-differentiative (229), anti-differentiative (76) or neither (571) using expression profiling data obtained in the FANTOM4 study. This classification analysis suggested that several factors could be involved in monocytic differentiation, while others such as MYB and the leukemogenic fusion MLL-MLLT3 could help to maintain the initial undifferentiated state by repressing the expression of pro-differentiative factors or maintaining expression of antidifferentiative factors.
doi:10.1186/gb-2009-10-11-r121 pmid:19883503 pmcid:PMC2810662 fatcat:7ippv5vryvbyzltusa4asrwt5q

Genome-wide investigation of in vivo EGR-1 binding sites in monocytic differentiation

Atsutaka Kubosaki, Yasuhiro Tomaru, Michihira Tagami, Erik Arner, Hisashi Miura, Takahiro Suzuki, Masanori Suzuki, Harukazu Suzuki, Yoshihide Hayashizaki
2009 Genome Biology  
Immediate early genes are considered to play important roles in dynamic gene regulatory networks following exposure to appropriate stimuli. One of the immediate early genes, early growth response gene 1 (EGR-1), has been implicated in differentiation of human monoblastoma cells along the monocytic commitment following treatment with phorbol ester. EGR-1 has been thought to work as a modifier of monopoiesis, but the precise function of EGR-1 in monocytic differentiation has not been fully
more » ... ted. Results: We performed the first genome-wide analysis of EGR-1 binding sites by chromatin immunoprecipitation with promoter array (ChIP-chip) and identified EGR-1 target sites in differentiating THP-1 cells. By combining the results with previously reported FANTOM4 data, we found that EGR-1 binding sites highly co-localized with CpG islands, acetylated histone H3 lysine 9 binding sites, and CAGE tag clusters. Gene Ontology (GO) analysis revealed enriched terms, including binding of molecules, in EGR-1 target genes. In addition, comparison with gene expression profiling data showed that EGR-1 binding influenced gene expression. Moreover, observation of in vivo occupancy changes of DNA binding proteins following PMA stimulation indicated that SP1 binding occupancies were dramatically changed near EGR-1 binding sites. Conclusions: We conclude that EGR-1 mainly recognizes GC-rich consensus sequences in promoters of active genes. GO analysis and gene expression profiling data confirm that EGR-1 is involved in initiation of information transmission in cell events. The observations of in vivo occupancy changes of EGR-1 and SP1 suggest that several types of interplay between EGR-1 and other proteins result in multiple responses to EGR-1 downstream genes.
doi:10.1186/gb-2009-10-4-r41 pmid:19374776 pmcid:PMC2688932 fatcat:exnrmpjbpndq7aelfmsyrv3o54

Core promoter structure and genomic context reflect histone 3 lysine 9 acetylation patterns

Anton Kratz, Erik Arner, Rintaro Saito, Atsutaka Kubosaki, Jun Kawai, Harukazu Suzuki, Piero Carninci, Takahiro Arakawa, Masaru Tomita, Yoshihide Hayashizaki, Carsten O Daub
2010 BMC Genomics  
Histone modifications play an important role in gene regulation. Acetylation of histone 3 lysine 9 (H3K9ac) is generally associated with transcription initiation and unfolded chromatin, thereby positively influencing gene expression. Deep sequencing of the 5' ends of gene transcripts using DeepCAGE delivers detailed information about the architecture and expression level of gene promoters. The combination of H3K9ac ChIP-chip and DeepCAGE in a myeloid leukemia cell line (THP-1) allowed us to
more » ... y the spatial distribution of H3K9ac around promoters using a novel clustering approach. The promoter classes were analyzed for association with relevant genomic sequence features. We performed a clustering of 4,481 promoters according to their surrounding H3K9ac signal and analyzed the clustered promoters for association with different sequence features. The clustering revealed three groups with major H3K9ac signal upstream, centered and downstream of the promoter. Narrow single peak promoters tend to have a concentrated activity of H3K9ac in the upstream region, while broad promoters tend to have a concentrated activity of H3K9ac and RNA polymerase II binding in the centered and downstream regions. A subset of promoters with high gene expression level, compared to subsets with low and medium gene expression, shows dramatic increase in H3K9ac activity in the upstream cluster only; this may indicate that promoters in the centered and downstream clusters are predominantly regulated at post-initiation steps. Furthermore, the upstream cluster is depleted in CpG islands and more likely to regulate un-annotated genes. Clustering core promoters according to their surrounding acetylation signal is a promising approach for the study of histone modifications. When examining promoters clustered into groups according to their surrounding H3K9 acetylation signal, we find that the relative localization and intensity of H3K9ac is very specific depending on characteristic sequence features of the promoter. Experimental data from DeepCAGE and ChIP-chip experiments using undifferentiated (monocyte) and differentiated (macrophage) THP-1 cells leads us to the same conclusions.
doi:10.1186/1471-2164-11-257 pmid:20409305 pmcid:PMC2867832 fatcat:kx7356v2pzaidbdjumde75drn4

A transient disruption of fibroblastic transcriptional regulatory network facilitatestrans-differentiation

Yasuhiro Tomaru, Ryota Hasegawa, Takahiro Suzuki, Taiji Sato, Atsutaka Kubosaki, Masanori Suzuki, Hideya Kawaji, Alistair R.R. Forrest, Yoshihide Hayashizaki, Jay W. Shin, Harukazu Suzuki
2014 Nucleic Acids Research  
Transcriptional Regulatory Networks (TRNs) coordinate multiple transcription factors (TFs) in concert to maintain tissue homeostasis and cellular function. The re-establishment of target cell TRNs has been previously implicated in direct trans-differentiation studies where the newly introduced TFs switch on a set of key regulatory factors to induce de novo expression and function. However, the extent to which TRNs in starting cell types, such as dermal fibroblasts, protect cells from undergoing
more » ... cellular reprogramming remains largely unexplored. In order to identify TFs specific to maintaining the fibroblast state, we performed systematic knockdown of 18 fibroblast-enriched TFs and analyzed differential mRNA expression against the same 18 genes, building a Matrix-RNAi. The resulting expression matrix revealed seven highly interconnected TFs. Interestingly, suppressing four out of seven TFs generated lipid droplets and induced PPARG and CEBPA expression in the presence of adipocyte-inducing medium only, while negative control knockdown cells maintained fibroblastic character in the same induction regime. Global gene expression analyses further revealed that the knockdown-induced adipocytes expressed genes associated with lipid metabolism and significantly suppressed fibroblast genes. Overall, this study reveals the critical role of the TRN in protecting cells against aberrant reprogramming, and demonstrates the vulnerability of donor cell's TRNs, offering a novel strategy to induce transgene-free trans-differentiations.
doi:10.1093/nar/gku567 pmid:25013174 pmcid:PMC4132712 fatcat:fd7zhl2zobgzbcklk3uexn4ujq

The Molecular Detection of Cryptosporidium and Giardia in Sika Deer (Cervus Nippon Centralis)in Japan

Akiko Yamazaki, Shinji Izumiyama, Kenji Yagita, Naohiro Kishida, Atsutaka Kubosaki, Yukiko Hara-Kudo, Yoichi Kamata, Jun Terajima
2018 Food Safety  
Fecal specimens (271 samples) from wild deer, Cervus nippon centralis, were collected from nine different areas in Japan; these samples were subjected to a real-time reverse transcription PCR for Cryptosporidium-and Giardia-specific 18S ribosomal RNA to investigate the prevalence of Cryptosporidium and Giardia infection. The incidence of Cryptosporidium and Giardia in the nine areas ranged from 0% to 20.0% and 0% to 3.4%, respectively. The prevalence of Cryptosporidium among male and female
more » ... was 8.1% and 3.9%, respectively, while that of Giardia was 0.7% and 0.8%. Sequence analysis identified the Cryptosporidium deer genotype, Cryptosporidium bovis, Cryptosporidium ryanae and Cryptosporidium meleagridis from the sequence of Cryptosporidium-specific partial 18S ribosomal RNA and Giardia intestinalis assemblage A from the partial sequence of Giardia-specific 18S rRNA. The variation in regional prevalence indicates that Cryptosporidium infection depends on environmental factors, and that bovine Cryptosporidium was detected more frequently than cervine Cryptosporidium. These data suggest that wild deer might be a healthy carrier of bovine Cryptosporidium.
doi:10.14252/foodsafetyfscj.2017029 pmid:32231952 pmcid:PMC6989202 fatcat:ve5kgehmone6zghpkontpll5ga

CpG site-specific alteration of hydroxymethylcytosine to methylcytosine beyond DNA replication

Atsutaka Kubosaki, Yasuhiro Tomaru, Erina Furuhata, Takahiro Suzuki, Jay W. Shin, Christophe Simon, Yoshinari Ando, Ryota Hasegawa, Yoshihide Hayashizaki, Harukazu Suzuki
2012 Biochemical and Biophysical Research Communications - BBRC  
Kubosaki et al. / Biochemical and Biophysical Research Communications 426 (2012) 141-147  ... 
doi:10.1016/j.bbrc.2012.08.053 pmid:22925887 fatcat:amh27my4tve4hlpixhu4hfcpyi

Nuclear Pore Complex Protein Mediated Nuclear Localization of Dicer Protein in Human Cells

Yoshinari Ando, Yasuhiro Tomaru, Ayako Morinaga, Alexander Maxwell Burroughs, Hideya Kawaji, Atsutaka Kubosaki, Ryuichiro Kimura, Maiko Tagata, Yoko Ino, Hisashi Hirano, Joe Chiba, Harukazu Suzuki (+3 others)
2011 PLoS ONE  
Human DICER1 protein cleaves double-stranded RNA into small sizes, a crucial step in production of single-stranded RNAs which are mediating factors of cytoplasmic RNA interference. Here, we clearly demonstrate that human DICER1 protein localizes not only to the cytoplasm but also to the nucleoplasm. We also find that human DICER1 protein associates with the NUP153 protein, one component of the nuclear pore complex. This association is detected predominantly in the cytoplasm but is also clearly
more » ... istinguishable at the nuclear periphery. Additional characterization of the NUP153-DICER1 association suggests NUP153 plays a crucial role in the nuclear localization of the DICER1 protein.
doi:10.1371/journal.pone.0023385 pmid:21858095 pmcid:PMC3156128 fatcat:zn7founsgvchfdlkprjzi32hau

Establishment of single-cell screening system for the rapid identification of transcriptional modulators involved in direct cell reprogramming

Jay W. Shin, Takahiro Suzuki, Noriko Ninomiya, Mami Kishima, Yuki Hasegawa, Atsutaka Kubosaki, Haruka Yabukami, Yoshihide Hayashizaki, Harukazu Suzuki
2012 Nucleic Acids Research  
Combinatorial interactions of transcription modulators are critical to regulate cell-specific expression and to drive direct cell reprogramming (e.g. trans-differentiation). However, the identification of key transcription modulators from myriad of candidate genes is laborious and time consuming. To rapidly identify key regulatory factors involved in direct cell reprogramming, we established a multiplex single-cell screening system using a fibroblastto-monocyte transition model. The system
more » ... ments a single-cell 'shotgun-transduction' strategy followed by nested-single-cell-polymerase chain reaction (Nesc-PCR) gene expression analysis. To demonstrate this, we simultaneously transduced 18 monocyte-enriched transcription modulators in fibroblasts followed by selection of single cells expressing monocyte-specific CD14 and HLA-DR cell-surface markers from a heterogeneous population. Highly multiplex Nesc-PCR expression analysis revealed a variety of gene combinations with a significant enrichment of SPI1 (86/86) and a novel transcriptional modulator, HCLS1 (76/86), in the CD14 + /HLA-DR + single cells. We could further demonstrate the synergistic role of HCLS1 in regulating monocyte-specific gene expressions and phagocytosis in dermal fibroblasts in the presence of SPI1. This study establishes a platform for a multiplex single-cell screening of combinatorial transcription modulators to drive any direct cell reprogramming.
doi:10.1093/nar/gks732 pmid:22879381 pmcid:PMC3505982 fatcat:zjema5y2qvadjnwuviwallyqsu

A New Protocol for the Detection of Sterigmatocystin-producing Aspergillus Section Versicolores Using a High Discrimination Polymerase

ATSUTAKA KUBOSAKI, NAOKI KOBAYASHI, MAIKO WATANABE, TOMOYA YOSHINARI, KOSUKE TAKATORI, YUTAKA KIKUCHI, YUKIKO HARA-KUDO, JUN TERAJIMA, YOSHIKO SUGITA-KONISHI
2020 Biocontrol Science  
Tel: +81-44-270-6573, E-mail: kubosaki (a) nihs.go.jp A. creber, A. jensenii, A. versicolor sensu stricto, A. venenatus, A. puulaauensis, and A. tennesseensis produced STC, and all 22 A. sydowii isolates  ... 
doi:10.4265/bio.25.113 pmid:32507789 fatcat:yr7wfpgkgjh4dnwo5yi5y7en3q

Reconstruction of Monocyte Transcriptional Regulatory Network Accompanies Monocytic Functions in Human Fibroblasts

Takahiro Suzuki, Mika Nakano-Ikegaya, Haruka Yabukami-Okuda, Michiel de Hoon, Jessica Severin, Satomi Saga-Hatano, Jay W. Shin, Atsutaka Kubosaki, Christophe Simon, Yuki Hasegawa, Yoshihide Hayashizaki, Harukazu Suzuki (+1 others)
2012 PLoS ONE  
Transcriptional regulatory networks (TRN) control the underlying mechanisms behind cellular functions and they are defined by a set of core transcription factors regulating cascades of peripheral genes. Here we report SPI1, CEBPA, MNDA and IRF8 as core transcription factors of monocyte TRN and demonstrate functional inductions of phagocytosis, inflammatory response and chemotaxis activities in human dermal fibroblasts. The Gene Ontology and KEGG pathway analyses also revealed notable
more » ... ion of genes involved in immune response and endocytosis in fibroblasts. Moreover, monocyte TRN-inducers triggered multiple monocyte-specific genes based on the transcription factor motif response analysis and suggest that complex cellular TRNs are uniquely amenable to elicit cell-specific functions in unrelated cell types.
doi:10.1371/journal.pone.0033474 pmid:22428058 pmcid:PMC3302774 fatcat:luhr2dtfnzg73nvfi6wd3lkyty

Comprehensive Fungal Community Analysis of House Dust using Next-Generation Sequencing

Kazuki Izawa, Atsutaka Kubosaki, Naoki Kobayashi, Yutaka Akiyama, Akiko Yamazaki, Kazuhiro Hashimoto, Rumi Konuma, Yoichi Kamata, Yukiko Hara-Kudo, Kenichi Hasegawa, Toshiharu Ikaga, Maiko Watanabe
2020 International Journal of Environmental Research and Public Health  
Fungal community analyses in homes have been attracting attention because fungi are now generally considered to be allergens. Currently, these analyses are generally conducted using the culture method, although fungal communities in households often contain species that are difficult to culture. In contrast, next-generation sequencing (NGS) represents a comprehensive, labor- and time-saving approach that can facilitate species identification. However, the reliability of the NGS method has not
more » ... en compared to that of the culture method. In this study, in an attempt to demonstrate the reliability of this application, we used the NGS method to target the internal transcribed spacer 1 (ITS1) in the fungal genome, conducted fungal community analyses for 18 house-dust samples and analyzed fungal community structures. The NGS method positively correlated with the culture method regarding the relative abundance of Aspergillus, Penicillium, Cladosporium and yeasts, which represent the major fungal components found in houses. Furthermore, several genera, such as Malassezia, could be sensitively detected. Our results imply that the reliability of the NGS method is comparable to that of the culture method and indicates that easily available databases may require modifications, including the removal of registrations that have not been sufficiently classified at the genus level.
doi:10.3390/ijerph17165842 pmid:32806670 pmcid:PMC7460106 fatcat:wya7y2ghcbai3aumq746hxxdiu

Insulin secretion in islets from mice with a double knockout for the dense core vesicle proteins islet antigen-2 (IA-2) and IA-2β

Jean-Claude Henquin, Myriam Nenquin, Andras Szollosi, Atsutaka Kubosaki, Abner Louis Notkins
2007 Journal of Endocrinology  
Mice with a double knockout for IA-2 and IA-2b were then produced (Kubosaki et al. 2005) .  ...  In contrast, the rapid increase in plasma insulin induced by arginine persisted (Kubosaki et al. 2005) .  ... 
doi:10.1677/joe-07-0496 pmid:18310453 fatcat:n4ben4ik6ja43jak54mkzauehe
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