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  • 1
    Publication Date: 2005-09-06
    Description: 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carninci, P -- Kasukawa, T -- Katayama, S -- Gough, J -- Frith, M C -- Maeda, N -- Oyama, R -- Ravasi, T -- Lenhard, B -- Wells, C -- Kodzius, R -- Shimokawa, K -- Bajic, V B -- Brenner, S E -- Batalov, S -- Forrest, A R R -- Zavolan, M -- Davis, M J -- Wilming, L G -- Aidinis, V -- Allen, J E -- Ambesi-Impiombato, A -- Apweiler, R -- Aturaliya, R N -- Bailey, T L -- Bansal, M -- Baxter, L -- Beisel, K W -- Bersano, T -- Bono, H -- Chalk, A M -- Chiu, K P -- Choudhary, V -- Christoffels, A -- Clutterbuck, D R -- Crowe, M L -- Dalla, E -- Dalrymple, B P -- de Bono, B -- Della Gatta, G -- di Bernardo, D -- Down, T -- Engstrom, P -- Fagiolini, M -- Faulkner, G -- Fletcher, C F -- Fukushima, T -- Furuno, M -- Futaki, S -- Gariboldi, M -- Georgii-Hemming, P -- Gingeras, T R -- Gojobori, T -- Green, R E -- Gustincich, S -- Harbers, M -- Hayashi, Y -- Hensch, T K -- Hirokawa, N -- Hill, D -- Huminiecki, L -- Iacono, M -- Ikeo, K -- Iwama, A -- Ishikawa, T -- Jakt, M -- Kanapin, A -- Katoh, M -- Kawasawa, Y -- Kelso, J -- Kitamura, H -- Kitano, H -- Kollias, G -- Krishnan, S P T -- Kruger, A -- Kummerfeld, S K -- Kurochkin, I V -- Lareau, L F -- Lazarevic, D -- Lipovich, L -- Liu, J -- Liuni, S -- McWilliam, S -- Madan Babu, M -- Madera, M -- Marchionni, L -- Matsuda, H -- Matsuzawa, S -- Miki, H -- Mignone, F -- Miyake, S -- Morris, K -- Mottagui-Tabar, S -- Mulder, N -- Nakano, N -- Nakauchi, H -- Ng, P -- Nilsson, R -- Nishiguchi, S -- Nishikawa, S -- Nori, F -- Ohara, O -- Okazaki, Y -- Orlando, V -- Pang, K C -- Pavan, W J -- Pavesi, G -- Pesole, G -- Petrovsky, N -- Piazza, S -- Reed, J -- Reid, J F -- Ring, B Z -- Ringwald, M -- Rost, B -- Ruan, Y -- Salzberg, S L -- Sandelin, A -- Schneider, C -- Schonbach, C -- Sekiguchi, K -- Semple, C A M -- Seno, S -- Sessa, L -- Sheng, Y -- Shibata, Y -- Shimada, H -- Shimada, K -- Silva, D -- Sinclair, B -- Sperling, S -- Stupka, E -- Sugiura, K -- Sultana, R -- Takenaka, Y -- Taki, K -- Tammoja, K -- Tan, S L -- Tang, S -- Taylor, M S -- Tegner, J -- Teichmann, S A -- Ueda, H R -- van Nimwegen, E -- Verardo, R -- Wei, C L -- Yagi, K -- Yamanishi, H -- Zabarovsky, E -- Zhu, S -- Zimmer, A -- Hide, W -- Bult, C -- Grimmond, S M -- Teasdale, R D -- Liu, E T -- Brusic, V -- Quackenbush, J -- Wahlestedt, C -- Mattick, J S -- Hume, D A -- Kai, C -- Sasaki, D -- Tomaru, Y -- Fukuda, S -- Kanamori-Katayama, M -- Suzuki, M -- Aoki, J -- Arakawa, T -- Iida, J -- Imamura, K -- Itoh, M -- Kato, T -- Kawaji, H -- Kawagashira, N -- Kawashima, T -- Kojima, M -- Kondo, S -- Konno, H -- Nakano, K -- Ninomiya, N -- Nishio, T -- Okada, M -- Plessy, C -- Shibata, K -- Shiraki, T -- Suzuki, S -- Tagami, M -- Waki, K -- Watahiki, A -- Okamura-Oho, Y -- Suzuki, H -- Kawai, J -- Hayashizaki, Y -- FANTOM Consortium -- RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group) -- TGM03P17/Telethon/Italy -- TGM06S01/Telethon/Italy -- New York, N.Y. -- Science. 2005 Sep 2;309(5740):1559-63.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16141072" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Base Sequence ; Conserved Sequence ; DNA, Complementary/chemistry ; *Genome ; Genome, Human ; Genomics ; Humans ; Mice/*genetics ; Promoter Regions, Genetic ; Proteins/genetics ; RNA/chemistry/classification ; RNA Splicing ; RNA, Untranslated/chemistry ; Regulatory Sequences, Ribonucleic Acid ; *Terminator Regions, Genetic ; *Transcription Initiation Site ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-03-29
    Description: Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andersson, Robin -- Gebhard, Claudia -- Miguel-Escalada, Irene -- Hoof, Ilka -- Bornholdt, Jette -- Boyd, Mette -- Chen, Yun -- Zhao, Xiaobei -- Schmidl, Christian -- Suzuki, Takahiro -- Ntini, Evgenia -- Arner, Erik -- Valen, Eivind -- Li, Kang -- Schwarzfischer, Lucia -- Glatz, Dagmar -- Raithel, Johanna -- Lilje, Berit -- Rapin, Nicolas -- Bagger, Frederik Otzen -- Jorgensen, Mette -- Andersen, Peter Refsing -- Bertin, Nicolas -- Rackham, Owen -- Burroughs, A Maxwell -- Baillie, J Kenneth -- Ishizu, Yuri -- Shimizu, Yuri -- Furuhata, Erina -- Maeda, Shiori -- Negishi, Yutaka -- Mungall, Christopher J -- Meehan, Terrence F -- Lassmann, Timo -- Itoh, Masayoshi -- Kawaji, Hideya -- Kondo, Naoto -- Kawai, Jun -- Lennartsson, Andreas -- Daub, Carsten O -- Heutink, Peter -- Hume, David A -- Jensen, Torben Heick -- Suzuki, Harukazu -- Hayashizaki, Yoshihide -- Muller, Ferenc -- FANTOM Consortium -- Forrest, Alistair R R -- Carninci, Piero -- Rehli, Michael -- Sandelin, Albin -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):455-61. doi: 10.1038/nature12787.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2]. ; 1] Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany [2] Regensburg Centre for Interventional Immunology (RCI), D-93042 Regensburg, Germany [3]. ; School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. ; The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark. ; 1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan. ; Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, C.F. Mollers Alle 3, Building 1130, DK-8000 Aarhus, Denmark. ; 1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2] The Finsen Laboratory, Rigshospitalet and Danish Stem Cell Centre (DanStem), University of Copenhagen, Ole Maaloes Vej 5, DK-2200, Denmark. ; Roslin Institute, Edinburgh University, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK. ; Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road MS 64-121, Berkeley, California 94720, USA. ; EMBL Outstation - Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [3] RIKEN Preventive Medicine and Diagnosis Innovation Program, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Preventive Medicine and Diagnosis Innovation Program, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan. ; Department of Biosciences and Nutrition, Karolinska Institutet, Halsovagen 7, SE-4183 Huddinge, Stockholm, Sweden. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [3] Department of Biosciences and Nutrition, Karolinska Institutet, Halsovagen 7, SE-4183 Huddinge, Stockholm, Sweden. ; Department of Clinical Genetics, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands. ; 1] Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany [2] Regensburg Centre for Interventional Immunology (RCI), D-93042 Regensburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670763" target="_blank"〉PubMed〈/a〉
    Keywords: *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation/*genetics ; Genetic Predisposition to Disease/genetics ; HeLa Cells ; Humans ; *Molecular Sequence Annotation ; *Organ Specificity ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/genetics ; RNA, Messenger/biosynthesis/genetics ; Transcription Initiation Site ; Transcription Initiation, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-03-29
    Description: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence/genetics ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Genes, Essential/genetics ; Genome/genetics ; Humans ; Mice ; *Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/analysis/genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-08-18
    Description: Classically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics are poorly understood. Using promoter-level expression profiling by non-biased deepCAGE we have studied the transcriptional dynamics of classically and alternatively activated macrophages. Transcription factor (TF) binding motif activity analysis revealed four motifs, NFKB1_REL_RELA, IRF1,2, IRF7 and TBP that are commonly activated but have distinct activity dynamics in M1 and M2 activation. We observe matching changes in the expression profiles of the corresponding TFs and show that only a restricted set of TFs change expression. There is an overall drastic and transient up-regulation in M1 and a weaker and more sustainable up-regulation in M2. Novel TFs, such as Thap6, Maff , (M1) and Hivep1, Nfil3, Prdm1 , (M2) among others, were suggested to be involved in the activation processes. Additionally, 52 (M1) and 67 (M2) novel differentially expressed genes and, for the first time, several differentially expressed long non-coding RNA (lncRNA) transcriptome markers were identified. In conclusion, the finding of novel motifs, TFs and protein-coding and lncRNA genes is an important step forward to fully understand the transcriptional machinery of macrophage activation.
    Keywords: Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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