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: Heaven scent: Finding may help restore fragrance to roses

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

Study on pesticides in lab rat feed causes a stir

Jul 02, 2015

French scientists published evidence Thursday of pesticide contamination of lab rat feed which they said discredited historic toxicity studies, though commentators questioned the analysis.

International consortium to study plant fertility evolution

Jul 02, 2015

Mark Johnson, associate professor of biology, has joined a consortium of seven other researchers in four European countries to develop the fullest understanding yet of how fertilization evolved in flowering plants. The research, ...

Making the biofuels process safer for microbes

Jul 02, 2015

A team of investigators at the University of Wisconsin-Madison and Michigan State University have created a process for making the work environment less toxic—literally—for the organisms that do the heavy ...

Why GM food is so hard to sell to a wary public

Jul 02, 2015

Whether commanding the attention of rock star Neil Young or apparently being supported by the former head of Greenpeace, genetically modified food is almost always in the news – and often in a negative ...

The hidden treasure in RNA-seq

Jul 01, 2015

Michael Stadler and his team at the Friedrich Miescher institute for Biomedical Research (FMI) have developed a novel computational approach to analyze RNA-seq data. By comparing intronic and exonic RNA reads, ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.