New maps for navigating genome unveiled by scientists
- Date:
- March 26, 2014
- Source:
- University of Edinburgh
- Summary:
- The clearest picture yet of how our genetic material is regulated in order to make the human body work has been built by an international team of scientists. They have mapped how a network of switches, built into our DNA, controls where and when our genes are turned on and off. The three year project has involved more than 250 scientists in more than 20 countries and regions.
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Scientists have built the clearest picture yet of how our genetic material is regulated in order to make the human body work. They have mapped how a network of switches, built into our DNA, controls where and when our genes are turned on and off.
University of Edinburgh scientists played a leading role in the international project -- called FANTOM5 -- which has been examining how our genome holds the code for creating the fantastic diversity of cell types that make up a human.
The three year project, steered by the RIKEN Center for Life Science Technologies in Japan, has involved more than 250 scientists in more than 20 countries and regions.
The study is a step change in our understanding of the human genome, which contains the genetic instructions needed to build and maintain all the many different cell types in the body. All of our cells contain the same instructions, but genes are turned on and off at different times in different cells.
This process is controlled by switches -- called promoters and enhancers -- found within the genome. It is the flicking of these switches that makes a muscle cell different to a liver or skin cell.
The team studied the largest ever set of cell types and tissues from human and mouse in order to identify the location of these switches within the genome. They also mapped where and when the switches are active in different cell types and how they interact with each other.
Today the consortium publishes a series of papers describing its findings, including a pair of landmark papers in the journal Nature.
In a separate study, researchers at the University of Edinburgh's Roslin Institute have used information from the atlas to investigate the regulation of an important set of genes that are required to build muscle and bone. Another study has used the atlas to investigate the regulation of genes in cells of the immune system.
The FANTOM5 project included major contributions from The Roslin Institute, which is funded by the Biotechnology and Biological Sciences Research Council, and the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh.
Professor David Hume, Director of The Roslin Institute and a lead researcher on the project, said: "The FANTOM5 project is a tremendous achievement. To use the analogy of an aeroplane, we have made a leap in understanding the function of all of the parts. And we have gone well beyond that, to understanding how they are connected and control the structures that enable flight.
"The FANTOM5 project has identified new elements in the genome that are the targets of functional genetic variations in human populations, and also have obvious applications to other species."
Dr Martin Taylor, from the MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, said: "The research gives us an insight as to why humans are different from other animals, even though we share many genes in common. Comparing the mouse and human atlases reveals extensive rewiring of gene switches that has occurred over time, helping us to understand more about how we have evolved."
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Journal References:
- Robin Andersson, Claudia Gebhard, Irene Miguel-Escalada, Ilka Hoof, Jette Bornholdt, Mette Boyd, Yun Chen, Xiaobei Zhao, Christian Schmidl, Takahiro Suzuki, Evgenia Ntini, Erik Arner, Eivind Valen, Kang Li, Lucia Schwarzfischer, Dagmar Glatz, Johanna Raithel, Berit Lilje, Nicolas Rapin, Frederik Otzen Bagger, Mette Jørgensen, Peter Refsing Andersen, Nicolas Bertin, Owen Rackham, A. Maxwell Burroughs, J. Kenneth Baillie, Yuri Ishizu, Yuri Shimizu, Erina Furuhata, Shiori Maeda, Yutaka Negishi, Christopher J. Mungall, Terrence F. Meehan, Timo Lassmann, Masayoshi Itoh, Hideya Kawaji, Naoto Kondo, Jun Kawai, Andreas Lennartsson, Carsten O. Daub, Peter Heutink, David A. Hume, Torben Heick Jensen, Harukazu Suzuki, Yoshihide Hayashizaki, Ferenc Müller, The FANTOM Consortium, Alistair R. R. Forrest, Piero Carninci, Michael Rehli, Albin Sandelin. An atlas of active enhancers across human cell types and tissues. Nature, 2014; 507 (7493): 455 DOI: 10.1038/nature12787
- Alistair R. R. Forrest, Hideya Kawaji, Michael Rehli, J. Kenneth Baillie, Michiel J. L. de Hoon, Vanja Haberle, Timo Lassmann, Ivan V. Kulakovskiy, Marina Lizio, Masayoshi Itoh, Robin Andersson, Christopher J. Mungall, Terrence F. Meehan, Sebastian Schmeier, Nicolas Bertin, Mette Jørgensen, Emmanuel Dimont, Erik Arner, Christian Schmidl, Ulf Schaefer, Yulia A. Medvedeva, Charles Plessy, Morana Vitezic, Jessica Severin, Colin A. Semple, Yuri Ishizu, Robert S. Young, Margherita Francescatto, Intikhab Alam, Davide Albanese, Gabriel M. Altschuler, Takahiro Arakawa, John A. C. Archer, Peter Arner, Magda Babina, Sarah Rennie, Piotr J. Balwierz, Anthony G. Beckhouse, Swati Pradhan-Bhatt, Judith A. Blake, Antje Blumenthal, Beatrice Bodega, Alessandro Bonetti, James Briggs, Frank Brombacher, A. Maxwell Burroughs, Andrea Califano, Carlo V. Cannistraci, Daniel Carbajo, Yun Chen, Marco Chierici, Yari Ciani, Hans C. Clevers, Emiliano Dalla, Carrie A. Davis, Michael Detmar, Alexander D. Diehl, Taeko Dohi, Finn Drabløs, Albert S. B. Edge, Matthias Edinger, Karl Ekwall, Mitsuhiro Endoh, Hideki Enomoto, Michela Fagiolini, Lynsey Fairbairn, Hai Fang, Mary C. Farach-Carson, Geoffrey J. Faulkner, Alexander V. Favorov, Malcolm E. Fisher, Martin C. Frith, Rie Fujita, Shiro Fukuda, Cesare Furlanello, Masaaki Furuno, Jun-ichi Furusawa, Teunis B. Geijtenbeek, Andrew P. Gibson, Thomas Gingeras, Daniel Goldowitz, Julian Gough, Sven Guhl, Reto Guler, Stefano Gustincich, Thomas J. Ha, Masahide Hamaguchi, Mitsuko Hara, Matthias Harbers, Jayson Harshbarger, Akira Hasegawa, Yuki Hasegawa, Takehiro Hashimoto, Meenhard Herlyn, Kelly J. Hitchens, Shannan J. Ho Sui, Oliver M. Hofmann, Ilka Hoof, Fumi Hori, Lukasz Huminiecki, Kei Iida, Tomokatsu Ikawa, Boris R. Jankovic, Hui Jia, Anagha Joshi, Giuseppe Jurman, Bogumil Kaczkowski, Chieko Kai, Kaoru Kaida, Ai Kaiho, Kazuhiro Kajiyama, Mutsumi Kanamori-Katayama, Artem S. Kasianov, Takeya Kasukawa, Shintaro Katayama, Sachi Kato, Shuji Kawaguchi, Hiroshi Kawamoto, Yuki I. Kawamura, Tsugumi Kawashima, Judith S. Kempfle, Tony J. Kenna, Juha Kere, Levon M. Khachigian, Toshio Kitamura, S. Peter Klinken, Alan J. Knox, Miki Kojima, Soichi Kojima, Naoto Kondo, Haruhiko Koseki, Shigeo Koyasu, Sarah Krampitz, Atsutaka Kubosaki, Andrew T. Kwon, Jeroen F. J. Laros, Weonju Lee, Andreas Lennartsson, Kang Li, Berit Lilje, Leonard Lipovich, Alan Mackay-sim, Ri-ichiroh Manabe, Jessica C. Mar, Benoit Marchand, Anthony Mathelier, Niklas Mejhert, Alison Meynert, Yosuke Mizuno, David A. de Lima Morais, Hiromasa Morikawa, Mitsuru Morimoto, Kazuyo Moro, Efthymios Motakis, Hozumi Motohashi, Christine L. Mummery, Mitsuyoshi Murata, Sayaka Nagao-Sato, Yutaka Nakachi, Fumio Nakahara, Toshiyuki Nakamura, Yukio Nakamura, Kenichi Nakazato, Erik van Nimwegen, Noriko Ninomiya, Hiromi Nishiyori, Shohei Noma, Tadasuke Nozaki, Soichi Ogishima, Naganari Ohkura, Hiroko Ohmiya, Hiroshi Ohno, Mitsuhiro Ohshima, Mariko Okada-Hatakeyama, Yasushi Okazaki, Valerio Orlando, Dmitry A. Ovchinnikov, Arnab Pain, Robert Passier, Margaret Patrikakis, Helena Persson, Silvano Piazza, James G. D. Prendergast, Owen J. L. Rackham, Jordan A. Ramilowski, Mamoon Rashid, Timothy Ravasi, Patrizia Rizzu, Marco Roncador, Sugata Roy, Morten B. Rye, Eri Saijyo, Antti Sajantila, Akiko Saka, Shimon Sakaguchi, Mizuho Sakai, Hiroki Sato, Hironori Satoh, Suzana Savvi, Alka Saxena, Claudio Schneider, Erik A. Schultes, Gundula G. Schulze-Tanzil, Anita Schwegmann, Thierry Sengstag, Guojun Sheng, Hisashi Shimoji, Yishai Shimoni, Jay W. Shin, Christophe Simon, Daisuke Sugiyama, Takaaki Sugiyama, Masanori Suzuki, Naoko Suzuki, Rolf K. Swoboda, Peter A. C. ’t Hoen, Michihira Tagami, Naoko Takahashi, Jun Takai, Hiroshi Tanaka, Hideki Tatsukawa, Zuotian Tatum, Mark Thompson, Hiroo Toyoda, Tetsuro Toyoda, Eivind Valen, Marc van de Wetering, Linda M. van den Berg, Roberto Verardo, Dipti Vijayan, Ilya E. Vorontsov, Wyeth W. Wasserman, Shoko Watanabe, Christine A. Wells, Louise N. Winteringham, Ernst Wolvetang, Emily J. Wood, Yoko Yamaguchi, Masayuki Yamamoto, Misako Yoneda, Yohei Yonekura,. A promoter-level mammalian expression atlas. Nature, 2014; 507 (7493): 462 DOI: 10.1038/nature13182
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