Transcription factor (TF) proteins act as switches that turn genes on and off, and the timing and localization of their activity ensures that genes are activated only when and where they are needed—an essential consideration in processes like embryonic development.
However, the TF–gene relationship is seldom simple. “In many cases, TFs work as complexes in which two or more proteins physically interact,” explains Harukazu Suzuki, project director at the RIKEN Omics Science Center, Yokohama, and scientific organizer of the international FANTOM4 Consortium. “Depending on the combination, expression of different sets of genes is regulated; thus, these protein–protein interactions are essential information for analysis of transcriptional network regulation.”
Both research organizations have made it their business to untangle these networks, and new work from Suzuki and collaborators provides a useful foundation for mapping functional TF associations1. The team generated protein-producing clones for a majority of the known transcription factors from humans and mice and used these to perform ‘two-hybrid’ experiments that reveal physical interactions between pairs of proteins in both species. An exhaustive screen of both pools of clones enabled the assembly of an ‘atlas’ of 762 and 877 likely TF–TF interactions in human and mouse, respectively, with subsequent experiments suggesting that these data potentially represent approximately one-quarter of all such interactions.
They then determined where each TF is produced in an effort to classify individual factors as tissue-localized ‘specifiers’ or broadly expressed ‘facilitators’. Further analysis enabled them to identify clusters of interactions associated with different subsets of tissues, revealing a fraction of TF–TF associations that help coordinate the development of embryonic tissue into the diverse range of cell types seen in mature organisms. “We identified a small protein–protein interaction sub-network consisting of only 15 TFs, which plays a crucial role in the regulation of cell fate,” says Suzuki. Strikingly, this network contained mostly promiscuously expressed ‘facilitators’, suggesting that the localization of multi-factor interactions is as important as the restricted expression of individual factors in governing tissue-specific gene expression.
Suzuki and colleagues hope to expand this ‘first draft’ atlas soon, and to explore the clinical implications of disruptions within these interaction networks. “We would like to expand the information to include diseased tissues and cells, and especially cancer,” he says. “[By comparing] these TF interaction networks to normal ones, we may be able to identify TFs involved in these diseases … and the [associated] interactions may offer novel targets for therapy.”
The corresponding author for this highlight is based at the LSA Technology Development Group, RIKEN Omics Science Center
1. Ravasi, T., Suzuki, H., Cannistraci, C.V., Katayama, S., Bajic, V.B., Tan, K., Akalin, A., Schmeier, S., Kanamori-Katayama, M., Bertin, N. et al. An atlas of combinatorial transcriptional regulation in mouse and man. Cell 140, 744–752 (2010)
gro-pr | Research asia research news
Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute
'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Life Sciences
27.10.2016 | Life Sciences
27.10.2016 | Power and Electrical Engineering