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First Genome-Wide Profiling of Transcription Start Sites in Drosophila melanogaster

13.05.2009
In an international effort, scientists at the Illinois Institute of Technology together with industrial partners at DNAFORM in Japan, imaGenes in Germany, FASTERIS in Switzerland, and Precision Biomarker Resources in USA have for the first time prepared a genome-wide map of Transcription Start Sites (TSS) for the fruit fly Drosophila melanogaster.

Drosophila is one of the best studied model organisms in biology and has greatly contributed to our understanding of genetics, development, physiology, and behavior.

With the increasing availability of genome sequences, research has shifted to transcriptome analysis for greater understanding of how genomic information is utilized in a regulated manner. Recent data mostly obtained by new Next-Generation Sequencing Methods indicate genome-wide RNA transcription from both DNA strands at unexpectedly high levels with complex overlapping patterns.

Of the different approaches to genome and transcriptome analysis, the Cap Analysis Gene Expression (CAGE) Method developed by the RIKEN Omics Center and DNAFORM, in combination with Next-Generation Sequencing is uniquely placed to experimentally identify TSS on a genome-wide level with the high accuracy and the precision required assessing such diverse expression patterns. After major contributions to the RIKEN FANTOM and NIH ENCODE projects, CAGE has now for the first time been applied to Drosophila melanogaster. Identification of TSS in Drosophila is a valuable contribution to what is already arguably the best annotated genome. The availability of genome sequences of 11 additional Drosophila species in combination with CAGE-identified TSS in Drosophila melanogaster promises great insights into evolutionary aspects of gene expression.

We expected most highly expressed CAGE tags to be linked to well annotated gene transcripts in Drosophila. However, initial analysis of our data shows only 25% of the highly expressed CAGE tag clusters map close to annotated TSS. CAGE studies of other organisms showed that about half of all genes have alternate promoters and/or transcripts originating within genes and distances upstream. That 75% of our highly expressed CAGE tag clusters are not tightly linked to known TSS even in the well annotated Drosophila genome suggests that transcription is much more complex than previously thought. Associating CAGE tags with exons and 3' UTRs, and linking transcripts to genes at variable distances away on both DNA strands will promise greater understanding of genome expression in Drosophila. Moreover, less highly expressed CAGE tag clusters point to wider expression of the Drosophila genome than described by the present annotation. Our study has thus potentially indentified new promoter sites for known genes as well as entirely new transcriptional events.

A unique advantage of the Drosophila system is that the worldwide Drosophila research community can rapidly test the implications of our new CAGE results. Molecular, genetic, developmental, and behavioral experiments on genes of particular interest will test the biological importance of newly detected promoter regions and the gene expression they drive. Considerable similarities have been found between flies and human, and results from Drosophila are expected to drive further advances in other species, including human.

About the Illinois Institute of Technology:
Founded in 1890, IIT is a PhD-granting university with more than 7,500 students in science, engineering, architecture, psychology, design, humanities, business and law. IIT's technology-focused curriculum is designed to advance knowledge through research and scholarship, and to prepare students from all over the world for professional achievement, service to society, and individual fulfillment. IIT's biology division has active graduate level research programs in a range of areas including genetics, molecular biology, biochemistry, and bioinformatics. A comprehensive overview can be found at http://www.iit.edu.
Contact:
Dr. Mitchell Dushay
BCPS, IIT, Life Sciences Building, 3101 S Dearborn St, Chicago, IL 60616 U.S.A.
Tel.: +1-312-567 8849 – e-mail: mdushay@iit.edu
About Precision Biomarker Inc.:
Precision Biomarker Resources provides automated, high-throughput microarray services using the latest Affymetrix GeneChip® Microarray and GeneChip® miRNA Array platforms to expedite the biologic investigations of pharmaceutical, biotechnology and academic researchers. Its founders’ experience and leadership in cancer studies and their commitment to advancing disease research give Precision Biomarker unique insight into the goals of drug and disease investigators who use genomics and genetics services for biomarker discovery. Precision accelerates research and drug development by providing targeted biomarker discovery services, including microarray and miRNA array processing, experimental design consultation and data analysis. The team’s expertise enhances every research and development stage, from discovery through preclinical, clinical and post-market studies. A comprehensive overview can be found at www.precisionbiomarker.com .
Contact:
Dr Eric Bremer, Chief Scientific Officer
Precision Biomarker Resources, Inc.
820 Davis Street, Suite 216
Evanston, Illinois 60201 USA
Tel: +1-874-866-0406 – email: ericgbremer@precisionbiomarker.com
About FASTERIS:
Fasteris (www.fasteris.com) is a leading provider of next-generation genomics services based in Geneva, Switzerland. Fasteris was the first service provider company to acquire an Illumina Genome Analyzer system in 2006. Its founders co-invented the “DNA Cluster” technology in 1996, which was later incorporated into the Illumina Genome Analyzer System. Being among the very first users of the system, Fasteris developed a very broad range of applications for the analysis of genetic variation and biological function. To help researchers extract the relevant genetic information from their samples we adapt our protocols from sample preparation to bioinformatics analyses. We provide highest quality service for a comprehensive range of applications such as ChIP-SEQ; small RNAs; Genomic Shotgun; mRNA-SEQ; or Gene Expression. For all these applications we provide “à la carte” Bioinformatics analyses. To reduce sequencing costs we developed Multiplexing: Bar-coding or Indexing to sequence several libraries in a single channel. Our customers around the world include leading genomic research centers, academic institutions, and biotechnology or pharmaceutical companies.
Contact:
Fasteris SA
Dr. Laurent Farinelli, Founder & Chief Executive Officer
P.O. Box 28- 1228 Plan-les-Ouates - Switzerland
Tel.: +41 22 794 22 23 – email: info@fasteris.com
SOURCE: Fasteris SA
About imaGenes :
imaGenes GmbH, Berlin, is a premier provider of genome research services in Europe and was founded in 2007 as a spin-off from RZPD (German Resource Center for Genome Research). imaGenes manages one of the most comprehensive collections of clones of mammalian and vertebrate genes in the world offered via its clone search engine GenomeCube®, linked to international databases. The imaGenes research services feature a broad range of microarray applications on Affymetrix, Agilent, and NimbleGen platforms as well as next generation sequencing services on an Illumina Genome Analyzer System. Researchers in academia and in the pharmaceutical industry are provided with highest quality resources and innovative technology with maximum flexibility and cost effectiveness. imaGenes is fully compliant with ISO 9001:2008 quality standards. A comprehensive overview can be found at www.imagenes-bio.de or www.rzpd.de
Contact:
imaGenes GmbH
Dr. Johannes Maurer – Director Genomic Products & Marketing
Robert-Rössle-Str. 10 / Erwin Negelein Building - 13125 Berlin - Germany
Tel.: +49-30-9489 2440 – e-mail: j.maurer@imagenes-bio.de
About DNAFORM:
K.K. DNAFORM was established as a venture company under a new initiative of the Institute of Physical and Chemical Research (RIKEN) for the utilization of the patented technologies developed by RIKEN scientists. With our commitment to innovative Precision Gene Technologies, developed together with the RIKEN Omics Center, we want to provide superior products and services for human diagnostics, food safety, and life science research. DNAFORM has provided the research community with RIKEN FANTOM Clones, established full-length cDNA cloning services, contributed to drug discovery by creating one of the world’s most comprehensive human full-length cDNA collection, and developed the new CAGE Methodology for next generation expression profiling along with genome annotation. With our innovative SMartAmp™ Detection Method we are now on the move to provide distinct solutions in Molecular Diagnostics and related applied markets. A comprehensive overview can be found at http://www.dnaform.jp
Contact:
K.K. DNAFORM
Dr. Matthias Harbers
Room 108, Leading Venture Plaza-2, 75-1, Ono-cho
Tsurumi-ku, Yokohama City, Kanagawa, 230-0046, Japan
Tel.: +81-45-510-0607 – e-mail: matthias.harbes@dnaform.jp

Dr. Mitchell Dushay | Newswise Science News
Further information:
http://www.iit.edu

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