Yoshiaki Tanaka

The University of Tokyo, Tokyo, Tokyo-to, Japan

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Publications (7)68.13 Total impact

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    ABSTRACT: The transcription factor Foxp3 is essential for the development of regulatory T (Treg) cells, yet its expression is insufficient for establishing the Treg cell lineage. Here we showed that Treg cell development was achieved by the combination of two independent processes, i.e., the expression of Foxp3 and the establishment of Treg cell-specific CpG hypomethylation pattern. Both events were induced by T cell receptor stimulation. The Treg cell-type CpG hypomethylation began in the thymus and continued to proceed in the periphery and could be fully established without Foxp3. The hypomethylation was required for Foxp3(+) T cells to acquire Treg cell-type gene expression, lineage stability, and full suppressive activity. Thus, those T cells in which the two events have concurrently occurred are developmentally set into the Treg cell lineage. This model explains how Treg cell fate and plasticity is controlled and can be exploited to generate functionally stable Treg cells.
    Immunity 10/2012; · 19.80 Impact Factor
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    ABSTRACT: We performed a genome-wide analysis of transcriptional start sites (TSSs) in human genes by multifaceted use of a massively parallel sequencer. By analyzing 800 million sequences that were obtained from various types of transcriptome analyses, we characterized 140 million TSS tags in 12 human cell types. Despite the large number of TSS clusters (TSCs), the number of TSCs was observed to decrease sharply with increasing expression levels. Highly expressed TSCs exhibited several characteristic features: Nucleosome-seq analysis revealed highly ordered nucleosome structures, ChIP-seq analysis detected clear RNA polymerase II binding signals in their surrounding regions, evaluations of previously sequenced and newly shotgun-sequenced complete cDNA sequences showed that they encode preferable transcripts for protein translation, and RNA-seq analysis of polysome-incorporated RNAs yielded direct evidence that those transcripts are actually translated into proteins. We also demonstrate that integrative interpretation of transcriptome data is essential for the selection of putative alternative promoter TSCs, two of which also have protein consequences. Furthermore, discriminative chromatin features that separate TSCs at different expression levels were found for both genic TSCs and intergenic TSCs. The collected integrative information should provide a useful basis for future biological characterization of TSCs.
    Genome Research 03/2011; 21(5):775-89. · 14.40 Impact Factor
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    ABSTRACT: Polarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infections, respectively. Jumonji domain containing-3 (Jmjd3), a histone 3 Lys27 (H3K27) demethylase, has been implicated in the activation of macrophages. Here we show that Jmjd3 is essential for M2 macrophage polarization in response to helminth infection and chitin, though Jmjd3 is dispensable for M1 responses. Furthermore, Jmjd3 (also known as Kdm6b) is essential for proper bone marrow macrophage differentiation, and this function depends on demethylase activity of Jmjd3. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited number of genes. Among them, we identified Irf4 as encoding a key transcription factor that controls M2 macrophage polarization. Collectively, these results show that Jmjd3-mediated H3K27 demethylation is crucial for regulating M2 macrophage development leading to anti-helminth host responses.
    Nature Immunology 10/2010; 11(10):936-44. · 26.20 Impact Factor
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    Yoshiaki Tanaka, Itsuki Yoshimura, Kenta Nakai
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    ABSTRACT: Although nucleosome remodeling is essential to transcriptional regulation in eukaryotes, little is known about its genome-wide behavior. Since a number of nucleosome positioning maps in vivo have been recently determined, we examined if their comparisons might be used for obtaining a genome-wide profile of nucleosome remodeling. Using seven yeast maps, the local variability of nucleosomes, measured by the entropy, was significantly higher in a set of reported unstable nucleosomes. The binding sites of four transcription factors, known as the remodeling factors, were distinctively high both in entropy and linker ratio, whereas those of Yhp1, their potential inhibitor, showed the lowest values in both of them. Taken together, our map shows the general information of nucleosome dynamics reasonably well. The "nucleosome dynamics" map provides the new significant correlation with the degree of expression variety instead of their intensity. Furthermore, the associations with gene function and histone modification were also discussed here.
    Chromosoma 03/2010; 119(4):391-404. · 3.34 Impact Factor
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    ABSTRACT: Understanding the genome sequence-specific positioning of nucleosomes is essential to understand various cellular processes, such as transcriptional regulation and replication. As a typical example, the 10-bp periodicity of AA/TT and GC dinucleotides has been reported in several species, but it is still unclear whether this feature can be observed in the whole genomes of all eukaryotes. With Fourier analysis, we found that this is not the case: 84-bp and 167-bp periodicities are prevalent in primates. The 167-bp periodicity is intriguing because it is almost equal to the sum of the lengths of a nucleosomal unit and its linker region. After masking Alu elements, these periodicities were greatly diminished. Next, using two independent large-scale sets of nucleosome mapping data, we analyzed the distribution of nucleosomes in the vicinity of Alu elements and showed that (1) there are one or two fixed slot(s) for nucleosome positioning within the Alu element and (2) the positioning of neighboring nucleosomes seems to be in phase, more or less, with the presence of Alu elements. Furthermore, (3) these effects of Alu elements on nucleosome positioning are consistent with inactivation of promoter activity in Alu elements. Our discoveries suggest that the principle governing nucleosome positioning differs greatly across species and that the Alu family is an important factor in primate genomes.
    BMC Genomics 01/2010; 11:309. · 4.40 Impact Factor
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    Yoshiaki Tanaka, Kenta Nakai
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    ABSTRACT: Nucleosome configuration in eukaryotic genomes is an important clue to clarify the mechanisms of regulation for various nuclear events. In the past few years, numerous computational tools have been developed for the prediction of nucleosome positioning, but there is no third-party benchmark about their performance. Here we present a performance evaluation using genome-scale in vivo nucleosome maps of two vertebrates and three invertebrates. In our measurement, two recently updated versions of Segal's model and Gupta's SVM with the RBF kernel, which was not implemented originally, showed higher prediction accuracy although their performances differ significantly in the prediction of medaka fish and candida yeast. The cross-species prediction results using Gupta's SVM also suggested rather specific characters of nucleosomal DNAs in medaka and budding yeast. With the analyses for over- and under-representat ion of DNA oligomers, we found both general and species-specific motifs in nucleosomal and linker DNAs. The oligomers commonly enriched in all five eukaryotes were only CA/TG and AC/GT. Thus, to achieve relatively high performance for a species, it is desirable to prepare the training data from the same species.
    Genome informatics. International Conference on Genome Informatics 10/2009; 23(1):169-78.