Bioinformatics Approaches for Determining the Functional Impact of Repetitive Elements on Non-coding RNAs.

With a large number of annotated non-coding RNAs (ncRNAs), repetitive sequences are found to constitute functional components (termed as repetitive elements) in ncRNAs that perform specific biological functions. Bioinformatics analysis is a powerful tool for improving our understanding of the role of repetitive elements in ncRNAs. This chapter summarizes recent findings that reveal the role of repetitive elements in ncRNAs.

Glycerol kinase stimulates uncoupling protein 1 expression by regulating fatty acid metabolism in beige adipocytes.

Browning of adipose tissue is induced by specific stimuli such as cold exposure and consists of up-regulation of thermogenesis in white adipose tissue. Recently, it has emerged as an attractive target for managing obesity in humans. Here, we performed a comprehensive analysis to identify genes associated with browning in murine adipose tissue.

Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells.

Background: Endothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood.

Common genetic variants associated with Parkinson's disease display widespread signature of epigenetic plasticity.

Parkinson disease (PD) is characterized by a pivotal progressive loss of substantia nigra dopaminergic neurons and aggregation of α-synuclein protein encoded by the SNCA gene. Genome-wide association studies identified almost 100 sequence variants linked to PD in SNCA. However, the consequences of this genetic variability are rather unclear.

Long non-coding RNA 2310069B03Rik functions as a suppressor of Ucp1 expression under prolonged cold exposure in murine beige adipocytes.

Specific conditions, such as exposure to cold, can induce the production of brown-like adipocytes in white adipose tissue. These adipocytes express high levels of uncoupling protein 1 (UCP1) and energy expended by generating heat. Thus, these are a potential target for the prevention or treatment of obesity.

Improvement of detection performance of fusion genes from RNA-seq data by clustering short reads.

Fusion genes are involved in cancer, and their detection using RNA-Seq is insufficient given the relatively short reading length. Therefore, we proposed a shifted short-read clustering (SSC) method, which focuses on overlapping reads from the same loci and extends them as a representative sequence. To verify their usefulness, we applied the SSC method to RNA-Seq data from four types of cell lines (BT-474, MCF-7, SKBR-3, and T-47D).

The dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin enhances brown adipose tissue function, thereby preventing obesity in mice.

To clarify the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor on whole-body energy metabolism, we treated mice fed a high-fat diet (HFD) with teneligliptin, a clinically available DPP-4 inhibitor. Teneligliptin significantly prevented HFD-induced obesity and obesity-associated metabolic disorders. It also increased oxygen consumption rate and upregulated uncoupling protein 1 (UCP1) expression in both brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT), suggesting that it enhances BAT function.

Characteristics of functional enrichment and gene expression level of human putative transcriptional target genes.

Background: Transcriptional target genes show functional enrichment of genes. However, how many and how significantly transcriptional target genes include functional enrichments are still unclear. To address these issues, I predicted human transcriptional target genes using open chromatin regions, ChIP-seq data and DNA binding sequences of transcription factors in databases, and examined functional enrichment and gene expression level of putative transcriptional target genes.

Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells.

Basophils and mast cells play critical roles in host defense against pathogens and allergic disorders. However, the molecular mechanism by which these cells are generated is not completely understood. Here we demonstrate that interferon regulatory factor-8 (IRF8), a transcription factor essential for the development of several myeloid lineages, also regulates basophil and mast cell development.

Essential role of the IRF8-KLF4 transcription factor cascade in murine monocyte differentiation.

Monocytes regulate host defenses, inflammation, and tissue homeostasis. The transcription factor interferon regulatory factor-8 (IRF8) stimulates monocyte/macrophage differentiation, yet genome-wide understanding of the differentiation program initiated by IRF8 is lacking. By combining chromatin immunoprecipitation sequencing with gene expression profiling, we show that during IRF8-dependent monocyte differentiation, IRF8 binding occurs at both promoter-proximal and promotor-distal regions together with the transcription factor PU.

Chromosome-biased binding and gene regulation by the Caenorhabditis elegans DRM complex.

DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we describe new aspects of DRM binding and function revealed through genome-wide analyses of the Caenorhabditis elegans DRM subunit LIN-54. We show that LIN-54 DNA-binding activity recruits DRM to promoters enriched for adjacent putative E2F/DP and LIN-54 binding sites, suggesting that these two DNA-binding moieties together direct DRM to its target genes.

The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts.

Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts.

Insertional mutagenesis by the Tol2 transposon-mediated enhancer trap approach generated mutations in two developmental genes: tcf7 and synembryn-like.

Gene trap and enhancer trap methods using transposon or retrovirus have been recently described in zebrafish. However, insertional mutants using these methods have not been reported. We report here development of an enhancer trap method by using the Tol2 transposable element and identification and characterization of insertional mutants.

The evolutionary emergence of cell type-specific genes inferred from the gene expression analysis of Hydra.

Cell lineages of cnidarians including Hydra represent the fundamental cell types of metazoans and provides us a unique opportunity to study the evolutionary diversification of cell type in the animal kingdom. Hydra contains epithelial cells as well as a multipotent interstitial cell (I-cell) that gives rise to nematocytes, nerve cells, gland cells, and germ-line cells. We used cDNA microarrays to identify cell type-specific genes by comparing gene expression in normal Hydra with animals lacking the I-cell lineage, so-called epithelial Hydra.

Transcriptional interferences in cis natural antisense transcripts of humans and mice.

For a significant fraction of mRNAs, their expression is regulated by other RNAs, including cis natural antisense transcripts (cis-NATs) that are complementary mRNAs transcribed from opposite strands of DNA at the same genomic locus. The regulatory mechanism of mRNA expression by cis-NATs is unknown, although a few possible explanations have been proposed. To understand this regulatory mechanism, we conducted a large-scale analysis of the currently available data and examined how the overlapping arrangements of cis-NATs affect their expression level.

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana.

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare.

A genome-wide and nonredundant mouse transcription factor database.

Here we describe the development of a genome-wide and nonredundant mouse transcription factor database and its viewer (http://genome.gsc.riken.

Identification of region-specific transcription factor genes in the adult mouse brain by medium-scale real-time RT-PCR.

We established a medium-scale real-time RT-PCR system focusing on transcription factors and applied it to their expression profiles in the adult mouse 11 brain regions (http://genome.gsc.riken.

Comprehensive analysis of NAC family genes in Oryza sativa and Arabidopsis thaliana.

The NAC domain was originally characterized from consensus sequences from petunia NAM and from Arabidopsis ATAF1, ATAF2, and CUC2. Genes containing the NAC domain (NAC family genes) are plant-specific transcriptional regulators and are expressed in various developmental stages and tissues. We performed a comprehensive analysis of NAC family genes in Oryza sativa (a monocot) and Arabidopsis thaliana (a dicot).

Antisense transcripts with rice full-length cDNAs.

Background: Natural antisense transcripts control gene expression through post-transcriptional gene silencing by annealing to the complementary sequence of the sense transcript. Because many genome and mRNA sequences have become available recently, genome-wide searches for sense-antisense transcripts have been reported, but few plant sense-antisense transcript pairs have been studied. The Rice Full-Length cDNA Sequencing Project has enabled computational searching of a large number of plant sense-antisense transcript pairs.

Collection, mapping, and annotation of over 28,000 cDNA clones from japonica rice.

We collected and completely sequenced 28,469 full-length complementary DNA clones from Oryza sativa L. ssp. japonica cv.

Antisense transcripts with FANTOM2 clone set and their implications for gene regulation.

We have used the FANTOM2 mouse cDNA set (60,770 clones), public mRNA data, and mouse genome sequence data to identify 2481 pairs of sense-antisense transcripts and 899 further pairs of nonantisense bidirectional transcription based upon genomic mapping. The analysis greatly expands the number of known examples of sense-antisense transcript and nonantisense bidirectional transcription pairs in mammals. The FANTOM2 cDNA set appears to contain substantially large numbers of noncoding transcripts suitable for antisense transcript analysis.

Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia.

We report the construction of the mouse full-length cDNA encyclopedia,the most extensive view of a complex transcriptome,on the basis of preparing and sequencing 246 libraries. Before cloning,cDNAs were enriched in full-length by Cap-Trapper,and in most cases,aggressively subtracted/normalized. We have produced 1,442,236 successful 3'-end sequences clustered into 171,144 groups, from which 60,770 clones were fully sequenced cDNAs annotated in the FANTOM-2 annotation.

A computer-based method of selecting clones for a full-length cDNA project: simultaneous collection of negligibly redundant and variant cDNAs.

We describe a computer-based method that selects representative clones for full-length sequencing in a full-length cDNA project. Our method classifies end sequences using two kinds of criteria, grouping, and clustering. Grouping places together variant cDNAs, family genes, and cDNAs with sequencing errors.