Singapore – (ACN Newswire) – Genome Institute of Singapore’s
(GIS) Associate Director of Genomic Technologies, Dr Yijun RUAN, led a
continuing study on the human genome spatial/structural configuration,
revealing how genes interact/communicate and influence each other, even when
they are located far away from each other. This discovery is crucial in
understanding how human genes work together, and will re-write textbooks on how
transcription regulation and coordination takes place in human cells.
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.
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
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.
Posted by Sean Fenske, Editor-in-Chief, MDT