DBTSS: database of transcription start sites, progress report 2008

Yamashita, Riu; Suzuki, Yutaka; Wakaguri, Hiroyuki; Tsuritani, Katsuki; Nakai, Kenta; Sugano, Sumio

doi:10.1093/nar/gkm901

Cited by 154 publications

(116 citation statements)

References 32 publications

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“…To predict putative TSSs in silico, we first used published data that describe human transcribed sequences, such as full-length cDNAs and 59-end cDNA sequence tags (Carninci et al 2005;Ruan et al 2007;Wakaguri et al 2007), which specify TSSs when aligned to the genome. We aligned a database of more than 250,000 human cDNAs and predicted about 37,000 gene models, with about 22,000 gene models represented by two or more cDNAs.…”

Section: Promoter Activity and Gene Expression Datamentioning

confidence: 99%

“…Sequence elements and nuclear proteins, including core promoter elements, enhancers, repressors, chromatin factors, and epigenetic modifications, interact to regulate the expression of genes. These interactions have been revealed through a large variety of methodologies, including global measurements of transcripts in different cell types (Carninci et al 2005;Harrow et al 2006;Wakaguri et al 2007), studies of proteins binding to DNA (The ENCODE Project Consortium 2007;Johnson et al 2007), measurements of enhancers in reporter genes in mice (Pennacchio et al 2006), measurements of DNA methylation (Weber et al 2007;Brunner et al 2009), and others (Trinklein et al 2003;Cooper et al 2006;The ENCODE Project Consortium 2007). Of the sequence elements that affect gene expression, transcriptional promoters have been the most widely studied in both prokaryotes and eukaryotes (Myers et al 1986).…”

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confidence: 99%

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Sequence features that drive human promoter function and tissue specificity

Landolin¹,

Johnson²,

Trinklein³

et al. 2010

Genome Res.

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Promoters are important regulatory elements that contain the necessary sequence features for cells to initiate transcription. To functionally characterize a large set of human promoters, we measured the transcriptional activities of 4575 putative promoters across eight cell lines using transient transfection reporter assays. In parallel, we measured gene expression in the same cell lines and observed a significant correlation between promoter activity and endogenous gene expression (r = 0.43). As transient transfection assays directly measure the promoting effect of a defined fragment of DNA sequence, decoupled from epigenetic, chromatin, or long-range regulatory effects, we sought to predict whether a promoter was active using sequence features alone. CG dinucleotide content was highly predictive of ubiquitous promoter activity, necessitating the separation of promoters into two groups: high CG promoters, mostly ubiquitously active, and low CG promoters, mostly cell line-specific. Computational models trained on the binding potential of transcriptional factor (TF) binding motifs could predict promoter activities in both high and low CG groups: average area under the receiver operating characteristic curve (AUC) of the models was 91% and exceeded the AUC of CG content by an average of 23%. Known relationships, for example, between HNF4A and hepatocytes, were recapitulated in the corresponding cell lines, in this case the liver-derived cell line HepG2. Half of the associations between tissue-specific TFs and cell line-specific promoters were new. Our study underscores the importance of collecting functional information from complementary assays and conditions to understand biology in a systematic framework.

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Section: Promoter Activity and Gene Expression Datamentioning

confidence: 99%

mentioning

confidence: 99%

Sequence features that drive human promoter function and tissue specificity

Landolin¹,

Johnson²,

Trinklein³

et al. 2010

Genome Res.

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“…Promoter sequences, 1000 base pairs upstream 9 and 200 base pairs downstream of the transcriptional start site, were retrieved from the « Database of Transcriptional Start Sites » (DBTSS) version 6 [33,34] and scanned for TFBS motifs using the Clover software and the TransFac 2008.4 position weight matrix (PWM) library [35]. Only high quality PWMs related to human transcription factors were used for in silico screening.…”

Section: Enrichment Analysis For In Silico Predicted Transcription Famentioning

confidence: 99%

Heteronemin, a spongean sesterterpene, inhibits TNFα-induced NF-κB activation through proteasome inhibition and induces apoptotic cell death

Schumacher

Cerella

Eifes

et al. 2010

Biochemical Pharmacology

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Heteronemin, a spongean sesterterpene, inhibits TNFα-induced NF-κB activation through proteasome inhibition and induces apoptotic cell death. Biochemical Pharmacology, Elsevier, 2009, 79 (4) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractIn this study, we investigated the biological effects of heteronemin, a marine sesterterpene isolated from the sponge Hyrtios sp. on chronic myelogenous leukemia cells. To gain further insight into the molecular mechanisms triggered by this compound, we initially performed DNA microarray profiling and determined which genes respond to heteronemin stimulation in TNF-treated cells and which genes display an interaction effect between heteronemin and TNF. Within the differentially regulated genes, we found that heteronemin was affecting cellular processes including cell cycle, apoptosis, mitogen-activated protein kinases (MAPKs) pathway and the nuclear factor B (NF-B) signaling cascade.We confirmed in silico experiments regarding NF-B inhibition by reporter gene analysis, electrophoretic mobility shift analysis and IB degradation. In order to assess the underlying molecular mechanisms, we determined that heteronemin inhibits both trypsin and chymotrypin-like proteasome activity at an IC 50 of 0.4 µM.Concomitant to the inhibition of the NF-B pathway, we also observed a reduction in cellular viability. Heteronemin induces apoptosis as shown by Annexin V/propidium iodide staining, nuclear morphology analysis, procaspase 3, -8 and -9 and poly(ADPribose) polymerase (PARP) cleavage as well as truncation of Bid. Altogether, resultsshow that this compound has potential as anti-inflammatory and anti-cancer agent.

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“…The 5' sequence of this gene has common features of housekeeping gene promoters. It lacks both TATA and CAAT boxes, has a high GC content and includes several potential Sp1 and AP2 consensus sites and >20 possible transcriptional start sites (6,7). However, up-regulation of TSG101 was found in thyroid papillary carcinomas, breast, ovarian and gastrointestinal tumors while down-regulation of TSG101 was observed in endometrial cancers (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Analysis of expression and structure of the TSG101 gene in cervical cancer cells

Broniarczyk

Olejnik-Schmidt²,

Łuczak³

et al. 2010

Int J Mol Med

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Abstract. Human papillomavirus (HPV)-mediated transformation of human epithelial cells has been recognized as a multi-step process in which additional unknown factors and (epi)genetic events are required. The tumor susceptibility gene 101 (TSG101) was discovered in mouse NIH3T3 fibroblast cells as a gene whose functional knockout leads to transformation. TSG101 protein is involved in a variety of important biological functions, such as ubiquitination, transcriptional regulation, endosomal trafficking, virus budding, proliferation and cell survival. It is suggested that TSG101 is an important factor for maintaining cellular homeostasis and that perturbation of TSG101 functions leads to cell transformation. Interestingly, a recent report showed up-or down-regulation of TSG101 in several human malignancies. At present, the role of TSG101 in cervical tumorigenesis is unexplained. TSG101 expression in tumors, where carcinogenesis is connected with viral infection, and a mechanism of TSG101 expression regulation in cancer cells are also unknown. The aim of our study was to estimate the TSG101 mRNA and protein level in cervical cancer and non-tumor epithelial cells. We also analyzed the TSG101 coding and promoter sequence using the PCR-SSCP technique and methylation pattern of the TSG101 promoter. Our real-time PCR and Western blot analysis showed decreased TSG101 mRNA and protein level in cervical cancer tissue in comparison to normal (non-tumor) HPV(-) and HPV16(+) epithelial cells. Our results suggest that TSG101 down-regulation in cervical cancer cells is not regulated by genetic or epigenetic events.However, we detected novel single nucleotide polymorphisms in the promoter of this gene.

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DBTSS: database of transcription start sites, progress report 2008

Cited by 154 publications

References 32 publications

Sequence features that drive human promoter function and tissue specificity

Sequence features that drive human promoter function and tissue specificity

Heteronemin, a spongean sesterterpene, inhibits TNFα-induced NF-κB activation through proteasome inhibition and induces apoptotic cell death

Analysis of expression and structure of the TSG101 gene in cervical cancer cells

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