Singapore Scientists Lead in 3D Mapping of Human Genome to Help Understand Human Diseases

The discovery was published in Cell, on 19 January 2012. The GIS is a research institute under the umbrella of the Agency for Science, Technology and Research (A*STAR).

Using a genomic technology invented by Dr Ruan and his team, called ChIA-PET, the Singapore-led international group, which is part of the ENCODE (ENCyclopedia Of DNA Elements) consortium, uncovered some of the fundamental mechanisms that regulate the gene expression in human cells.

“Scientists have always tried to understand how the large number of genes in an organism is regulated and coordinated to carry out the genetic programs encoded in the genome for cellular functions in our cells. It had been viewed that genes in higher organisms were individually expressed, while multiple related genes in low organisms like bacteria were arranged linearly together as operon and transcribed in single unit,” Dr Ruan explained.

“The new findings in this study revealed that although genes in human genomes are located far away from each other, related genes are in fact organised through long-range chromatin interactions and higher-order chromosomal conformations. This suggests a topological basis akin to the bacteria operon* system for coordinated transcription regulation. This topological mechanism for transcription regulation and coordination also provides insights to understand genetic elements that are involved in human diseases.”

GIS' executive director Prof Huck Hui NG said: “This is an important study that sheds light on the complex regulation of gene expression. Yijun's team continues to use the novel method of Chromatin Interaction Analysis with Paired-End-Tag sequencing to probe the higher order interactions of chromatin to discover new regulatory interactions between genes.”

“This publication describes ground-breaking work by Dr Yijun Ruan and his team at Genome Institute of Singapore,” added Dr Edward Rubin, Director of the Joint Genome Institute in US. “They address the fundamental question of how communication occurs between genes and their on and off switches in the human genome. Using a long range DNA mapping technology called ChIA-PET, the study reveals in three dimensional space that genes separated linearly by enormous distances in the human genome can come to lie next to each other in the cell when it is time for them to become active.

“I expect this study to move rapidly from primary scientific literature to textbooks describing for future students the operating principles of the human genome. The ChIA-PET technology, that is the telescope used in this exploration of the human genome, is an innovative and powerful molecular technology invented by Dr Ruan and his collaborators.”

The ENCODE is an ongoing project which was awarded to Dr Ruan's team by the National Human Genome Research Institute (NHGRI), an institute belonging to the National Institutes of Health (NIH, USA). The project was set up in 2003 with the aim of discovering all functional elements in the human genome to gain a deeper understanding of human biology and develop new strategies for preventing and treating diseases. So far Dr Ruan's team has received over US$2 million towards this project.

*In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter.

Notes to the Editor:

Research publication:
The research findings described in the press release can be found in the 19 January 2011 advanced online issue of Cell under the title “Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation”.
Authors:
Guoliang Li (1,10), Xiaoan Ruan (1,10), Raymond K. Auerbach (2,10), Kuljeet Singh Sandhu (1,10), Meizhen Zheng (1), Ping Wang (1), Huay Mei Poh (1), Yufen Goh (1), Joanne Lim (1), Jingyao Zhang (1), Hui Shan Sim (1), Su Qin Peh (1), Fabianus Hendriyan Mulawadi (1), Chin Thing Ong (1), Yuriy L. Orlov (1), Shuzhen Hong (1), Zhizhuo Zhang (3), Steve Landt (4), Debasish Raha (4), Ghia Euskirchen (4), Chia-Lin Wei (1), Weihong Ge (5), Huaien Wang (6), Carrie Davis (6), Katherine Fisher (7), Ali Mortazavi (7), Mark Gerstein (2), Thomas Gingeras (6), Barbara Wold (7), Yi Sun (5), Melissa J. Fullwood (1), Edwin Cheung (1,8), Edison Liu (1), Wing-Kin Sung (1,3), Michael Snyder (4,*), and Yijun Ruan (1,9,*).
1. Genome Institute of Singapore, 138672, Singapore
2. Program in Computational Biology and Departments of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
3. Department of Computer Science, School of Computing, National University of Singapore, 117417, Singapore
4. Center for Genomics and Personalized Medicine, Department of Genetics, Stanford University, Stanford, CA 94305, USA
5. Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA
6. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11797, USA
7. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
8. School of Biological Sciences, Nanyang Technological University, Singapore 637551
9.. College of Life Sciences, Huazhong Agricultural University, Wuhan 430070, China
10. These authors contributed equally to this work
*Correspondence: mpsnyder@stanford.edu (M.S.), ruanyj@gis.a-star.edu.sg (Y.R.)
About the Genome Institute of Singapore
The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact. www.gis.a-star.edu.sg.

About A*STAR

The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.. A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners. For more information about A*STAR, please visit www.a-star.edu.sg.

Contact:

Winnie Lim
Genome Institute of Singapore
Office of Corporate Communications
Tel: +65 6808 8013
Email: limcp2@gis.a-star.edu.sg