http://metadb.riken.jp/metadb/db/SciNetS_ria187i Functional Annotation of the Mammalian Genome 4 In FANTOM4 the focus has changed to understanding how these components work together in the context of a biological network. Using deepCAGE (deep sequencing with CAGE) we monitored the dynamics of transcription start site (TSS) usage during a time course of monocytic differentiation in the acute myeloid leukemia cell line THP-1. This allowed us to identify active promoters, monitor their relative expression and define relevant regions for carrying out transcription factor binding site predictions. Computational methods were then used to build a network model of gene expression in this leukemia and the transcription factors key to its regulation. This work gives the first picture of the wiring between genes involved in acute myeloid leukemia and provides a strategy for identifying key factors that determine cell fates.In addition to the network, FANTOM4 data was used in two additional analyses. The first identified a novel class of short RNAs associated with transcription start sites and the second focused on the role of repetitive element expression in the transcriptome. <div id="wrap"><a href="http://metadb.riken.jp/metadb/db/SciNetS_ria254i"><img src="http://metadb.riken.jp/dbfiles/SciNetS_ria187i/RIDM-ICON.jpg" title="to The RIKEN integrated database of mammals" class="image " style="margin-bottom: 2px;" width="300px" height="32px"></a> <div id="head"> <h1>FANTOM-4</h1> <h2>(Functional Annotation of Mammalian Genome)</h2> </div> <div id="content"><!--h3>Related RIKEN Databases:</h3><table><tbody><tr><td><a href="../ria254i/"><img src="http://metadb.riken.jp/dbfiles/SciNetS_ria187i/b_RIDM.jpg" style="margin-top: 5px;" border="0" width="173" height="48"></a></td><td><br></td><td><a href="../ria237i/"><img src="http://metadb.riken.jp/dbfiles/SciNetS_ria187i/b_CDTDB.jpg" style="margin-top: 5px;" border="0" width="173" height="48"></a></td><td><a href="../rib185i/"><img src="http://metadb.riken.jp/dbfiles/SciNetS_ria187i/b_MGI.jpg" style="margin-top: 5px;" border="0" width="173" height="48"></a></td><td><a href="../rib178i/"><img src="http://metadb.riken.jp/dbfiles/SciNetS_ria187i/b_Ensemble.jpg" style="margin-top: 5px;" border="0" width="173" height="48"></a></td></tr><tr><td><br></td><td><ul><li><strong><a href="http://fantom.gsc.riken.jp/4/gev/gbrowse/">Genome Browser</a></strong></li><li><strong><a href="http://fantom.gsc.riken.jp/4/edgeexpress/about/">Edge Express DB</a></strong></li></ul></td><td><br></td><td><br></td><td><br></td></tr></tbody></table><br--><div style="float: left; width: 460px; margin-bottom: 10px;"><h3>FANTOM4 Original Website</h3><table><tbody><tr><td valign="top"><div style="margin-top: 5px;"> please visit:</div></td><td><a href="http://fantom.gsc.riken.jp/4/"><img src="http://metadb.riken.jp/dbfiles/SciNetS_ria187i/fantomlogo.png" style="margin-top: 5px;" width="173" border="0" height="48"></a></td></tr><!--tr><td><br></td><td><a href="http://fantom.gsc.riken.jp/4/">http://fantom.gsc.riken.jp/4/</a></td></tr--><tr><td><br></td><td> ┣<a href="http://fantom.gsc.riken.jp/4/gev/gbrowse/">Genome Browser</a></td></tr><tr><td><br></td><td> ┗<a href="http://fantom.gsc.riken.jp/4/edgeexpress/about/">Edge Express DB</a></td></tr></tbody></table></div><div style="clear: both;"><h3>Description</h3><p>The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line</p></div><!--<h3>Investigation Title</h3><p>The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line</p>--><!--<h3>Investigation Description</h3>--><p>We analyzed transcriptional control in the human monocytic cell line THP-1 throughout a time course of differentiation. A new deep sequencing technology (deepCAGE) together with microarray analysis provided an integrated picture of promoter (deepCAGE) and mRNA expression over time. Comparative genomic regulatory site prediction and modeling the activities of regulatory motifs through time identified the key transcription factors driving differentiation, their time-dependent activities, and their target genes. Systematic siRNA knockdown of 52 key transcription factors confirmed the role of individual factors in the differentiation process. This analysis has therefore mapped a suite of transcription factors required for the maintenance of the undifferentiated state and for the transition from proliferation to differentiation.</p><!--<h3>Experiment Description</h3>--><p>The human monocytic cell line THP-1 throughout a time course of differentiation was profiled by deepCAGE together with microarray and ChIP/chip analysis. Systematic siRNA knockdown of 52 key transcription factors are perfomed, with following micorarray analysis. </p><!--<div> <div class="left"> <h3>Affiliation</h3> <p align="center">The FANTOM Consortium<br> Omics Science Center, RIKEN Yokohama Institute</p> </div> <div class="center"> <h3>E-mail</h3> <p align="center">fantom-help at gsc.riken.jp<br> rgscerg at gsc.riken.jp</p> </div> <div class="right"> <h3>Address</h3> <p align="center">1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan</p> </div></div>--><div style="clear: both;"></div></div></div> http://fantom.gsc.riken.jp/4/ FANTOM4では、ゲノム上に同定された要素同士が互いにどのように作用しているかというネットワークの解明に取り組みました。ヒト白血病由来細胞株(THP-1)が単芽球様から単球様に変化する際の、転写開始点(TSS)の動態をdeepCAGE法(deep sequencing with CAGE)により経時的に測定した結果、それぞれの時点において活性なプロモーターと、その発現量をモニタすることができました。これらのデータから転写因子結合部位をコンピューター解析により予測し、THP-1における転写制御ネットワークの一部を明らかにするとともに、この分化において支配的な役割を果たす転写因子を抽出することに成功しました。 転写制御ネットワークの他にも、FANTOM4で取得されたデータを解析することで、転写開始点に関連する短鎖RNAの発見、および、ゲノム配列中に数多く存在する反復配列の役割に関する新たな発見に結びつきました。 FANTOM4 FANTOM4