Showing papers by "Hiroki R. Ueda published in 2005"

The Transcriptional Landscape of the Mammalian Genome

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.

System-level identification of transcriptional circuits underlying mammalian circadian clocks.

Abstract: Mammalian circadian clocks consist of complexly integrated regulatory loops, making it difficult to elucidate them without both the accurate measurement of system dynamics and the comprehensive identification of network circuits. Toward a system-level understanding of this transcriptional circuitry, we identified clock-controlled elements on 16 clock and clock-controlled genes in a comprehensive surveillance of evolutionarily conserved cis elements and measurement of their transcriptional dynamics. Here we report the roles of E/E' boxes, DBP/E4BP4 binding elements and RevErbA/ROR binding elements in nine, seven and six genes, respectively. Our results indicate that circadian transcriptional circuits are governed by two design principles: regulation of E/E' boxes and RevErbA/ROR binding elements follows a repressor-precedes-activator pattern, resulting in delayed transcriptional activity, whereas regulation of DBP/E4BP4 binding elements follows a repressor-antiphasic-to-activator mechanism, which generates high-amplitude transcriptional activity. Our analysis further suggests that regulation of E/E' boxes is a topological vulnerability in mammalian circadian clocks, a concept that has been functionally verified using in vitro phenotype assay systems.

Principles in the Evolution of Metabolic Networks

Abstract: Understanding design principles of complex cellular organization is one of the major challenges in biology. Recent analysis of the large-scale cellular organization has revealed the scale-free nature and robustness of metabolic and protein networks. However, the underlying evolutional process that creates such a cellular organization is not fully elucidated. To approach this problem, we analyzed the metabolic networks of 126 organisms, whose draft or complete genome sequences have been published. This analysis has revealed that the evolutional process of metabolic networks follows the same and surprisingly simple principles in Archaea, Bacteria and Eukaryotes; where highly linked metabolites change their chemical links more dynamically than less linked metabolites. Here we demonstrate that this rich-travel-more mechanism rather than the previously proposed rich-get-richer mechanism can generate the observed scale-free organization of metabolic networks. These findings illustrate universal principles in evolution of metabolic networks and suggest marked flexibility of metabolic network throughout evolution.

Measurement system of the γ-ray angular distributions of the C(α,γ)12O16 reaction

Abstract: A new system to measure the γ -ray angular distributions of the C ( α , γ ) 12 O 16 reaction has been installed at the 3.2 MV Pelletron accelerator laboratory at Tokyo Institute of Technology. An intense 2.27 MeV α -beam with the pulse width of 1.9 ns was used to study the performance of the system. The γ -rays from the C ( α , γ ) 12 O 16 reaction were detected with three high-efficiency anti-Compton NaI(Tl) spectrometers, and they were well separated from neutron background from the C ( α , n ) 13 O 16 reaction using a time of flight method. The present study has demonstrated high sensitivity of the system to measure the γ -ray angular distributions of the C ( α , γ ) 12 O 16 reaction at low energy, and to determine both E1 and E2 cross-sections.