DNA's twisted communication: Genome organization key element for control of gene expression

Feb 28, 2013

During embryo development, genes are dynamically, and very precisely, switched on and off to confer different properties to different cells and build a well-proportioned and healthy animal. Fgf8 is one of the key genes in this process, controlling in particular the growth of the limbs and the formation of the different regions of the brain. Researchers at EMBL have elucidated how Fgf8 in mammal embryos is, itself, controlled by a series of multiple, interdependent regulatory elements. Their findings, published today in Developmental Cell, shed new light on the importance of the genome structure for gene regulation.

Fgf8 is controlled by a large number of that are clustered in the same large region of the genome and are interspersed with other, unrelated genes. Both the sequences and the intricate genomic arrangement of these elements have remained very stable throughout evolution, thus proving their importance. By selectively changing the relative positioning of the regulatory elements, the researchers were able to modify their combined impact on Fgf8, and therefore drastically affect the embryo.

"We showed that the surprisingly complex organisation of this genomic region is a key aspect of the regulation of Fgf8," explains François Spitz, who led the study at EMBL. "Fgf8 responds to the input of specific regulatory elements, and not to others, because it sits at a special place, not because it is a special gene. How the regulatory elements contribute to activate a gene is not determined by a specific recognition tag, but by where precisely the gene is in the genome."

Scientists are still looking into the molecular details of this . It is likely that the way DNA folds in 3D could, under certain circumstances, bring different sets of regulatory elements in contact with each other and with Fgf8, to trigger or prevent . These findings highlight a level of complexity of that is often overlooked. Regulatory elements are not engaged in a one-to-one relationship with the specific gene that has the appropriate DNA sequence. The local genomic organisation, and 3D folding of DNA, might actually be more important factors that both modulate the action of regulation elements, and put them in contact with their target gene.

More research will be necessary to understand in detail the impact of the 3D structure of DNA on the communication between the various elements of the genome, and on the regulation of gene expression. Further down the line, this could also further our understanding of how genomic rearrangements might disrupt these 3D regulatory networks and lead to diseases and malformations.

Explore further: Chickens to chili peppers: Scientists search for the first genetic engineers

Related Stories

The informant: A jumping gene

Mar 21, 2011

Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have developed a new method for studying gene regulation, by employing a jumping gene as an informant. Published online today in Nature ...

Mobile MITEs jump to fame in gene regulation

Jun 18, 2012

Moving genetic elements from one location to another in a genome makes for a very dynamic situation in terms of development and disease. An EU project has investigated a special type of micro transposable ...

Gene switch for odorant receptors

Nov 11, 2011

The olfactory sensory neurons in the nasal mucosa perceive the myriad smells in the air with the aid of odorant receptors. Each sensory neuron chooses one and only one receptor gene for expression. The probability ...

Recommended for you

Deadly human pathogen Cryptococcus fully sequenced

9 hours ago

Within each strand of DNA lies the blueprint for building an organism, along with the keys to its evolution and survival. These genetic instructions can give valuable insight into why pathogens like Cryptococcus ne ...

Building better soybeans for a hot, dry, hungry world

Apr 16, 2014

(Phys.org) —A new study shows that soybean plants can be redesigned to increase crop yields while requiring less water and helping to offset greenhouse gas warming. The study is the first to demonstrate ...

User comments : 0

More news stories

Deadly human pathogen Cryptococcus fully sequenced

Within each strand of DNA lies the blueprint for building an organism, along with the keys to its evolution and survival. These genetic instructions can give valuable insight into why pathogens like Cryptococcus ne ...

Biologists help solve fungi mysteries

(Phys.org) —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Better thermal-imaging lens from waste sulfur

Sulfur left over from refining fossil fuels can be transformed into cheap, lightweight, plastic lenses for infrared devices, including night-vision goggles, a University of Arizona-led international team ...

Hackathon team's GoogolPlex gives Siri extra powers

(Phys.org) —Four freshmen at the University of Pennsylvania have taken Apple's personal assistant Siri to behave as a graduate-level executive assistant which, when asked, is capable of adjusting the temperature ...