Hideaki Konno

Genome-wide analysis of mammalian promoter architecture and evolution

Mammalian promoters can be separated into two classes, conserved TATA box–enriched promoters, which initiate at a well-defined site, and more plastic, broad and evolvable CpG-rich promoters. We have sequenced tags corresponding to several hundred thousand transcription start sites (TSSs) in the mouse and human genomes, allowing precise analysis of the sequence architecture and evolution of distinct promoter classes. Different tissues and families of genes differentially use distinct types of promoters. Our tagging methods allow quantitative analysis of promoter usage in different tissues and show that differentially regulated alternative TSSs are a common feature in protein-coding genes and commonly generate alternative N termini. Among the TSSs, we identified new start sites associated with the majority of exons and with 3′ UTRs. These data permit genome-scale identification of tissue-specific promoters and analysis of the cis-acting elements associated with them.

Functional annotation of a full-length mouse cDNA collection

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Delineating developmental and metabolic pathways in vivo by expression profiling using the RIKEN set of 18,816 full-length enriched mouse cDNA arrays

We have systematically characterized gene expression patterns in 49 adult and embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs. Cluster analysis defined sets of genes that were expressed ubiquitously or in similar groups of tissues such as digestive organs and muscle. Clustering of expression profiles was observed in embryonic brain, postnatal cerebellum, and adult olfactory bulb, reflecting similarities in neurogenesis and remodeling. Finally, clustering genes coding for known enzymes into 78 metabolic pathways revealed a surprising coordination of expression within each pathway among different tissues. On the other hand, a more detailed examination of glycolysis revealed tissue-specific differences in profiles of key regulatory enzymes. Thus, by surveying global gene expression by using microarrays with a large number of elements, we provide insights into the commonality and diversity of pathways responsible for the development and maintenance of the mammalian body plan.

Comprehensive sequence analysis of translation termination sites in various eukaryotes

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.

Prediction of human cDNA from its homologous mouse full-length cDNA and human shotgun database.

We propose a prediction method for human full‐length cDNA by comparing sequence data between human genome shotgun sequence and mouse full‐length cDNA. The human genome which is homologous to the mouse full‐length cDNA is selected by a homology search program, and the predicted exons are connected at the exon‐intron junction which gives the best homology score to the mouse full‐length cDNA. The accuracy of the predicted human full‐length coding region is 83.3%, and the false positive rate is 16.7%. Five human full‐length proteins out of 20 proteins are correctly predicted.

Erratum: Genome-wide analysis of mammalian promoter architecture and evolution (Nature Genetics (2006) 38, (626-635))

Nat. Genet. 38, 626–635 (2006); published online 28 April 2006; corrected online 5 May 2006; corrected after print 29 August 2007 In the version of this article initially published, two of the smaller bar plots in Figure 1e were mistakenly duplicated. Specifically, the Zfp385 plot is an erroneous copy of the 137774 plot, and the Txndc7 plot is an erroneous copy of the Pik3r5 plot.

Corrigendum to: Prediction of human cDNA from its homologous mouse full‐length cDNA and human shotgun database

Corrigendum to: Prediction of human cDNA from its homologous mouse full-length cDNA and human shotgun database [FEBS Letters 464 (1999) 129^132]1 Yoshifumi Fukunishia;b;*, Harukazu Suzukia, Masayasu Yoshinoa, Hideaki Konnoa;b, Yoshihide Hayashizakia;b aLaboratory for Genome Exploration Research Group, Genomic Sciences Center (GSC) and Genome Science Laboratory, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan bCREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (JST), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan