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Blue dye indicates Fgf8 activity in regulatory regions of a mouse embryo.
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DNA’s Twisted Communication
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 fetus. Fgf8 is one of the key genes in this process, in particular controlling the growth of the limbs and the formation of the different regions of the brain
Researchers at The European Molecular Biology Laboratory (EMBL) explain 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 regulatory elements
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, researchers were able to modify
their combined impact on Fgf8, and 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.”
François Spitz
leader of the study at EMBL
Scientists are still looking into the molecular details of this regulatory mechanism. 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
An integrated holo-enhancer unit defines tissue- and gene specificity of the Fgf8 regulatory landscape - Mirna Marinic, Tugce Aktas, Sandra Ruf, and Francois Spitz – Advanced online publication in Developmental Cell on the 28 February 2013
About EMBL
The European Molecular Biology Laboratory is a basic research institute funded by public research monies from 20 member states (Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom) and associate member state Australia. Research at EMBL is conducted by approximately 85 independent groups covering the spectrum of molecular biology. The Laboratory has five units: the main Laboratory in Heidelberg, and Outstations in Hinxton (the European Bioinformatics Institute), Grenoble, Hamburg, and Monterotondo near Rome. The cornerstones of EMBL’s mission are: to perform basic research in molecular biology; to train scientists, students and visitors at all levels; to offer vital services to scientists in the member states; to develop new instruments and methods in the life sciences and to actively engage in technology transfer activities. Around 190 students are enrolled in EMBL’s International PhD programme. Additionally, the Laboratory offers a platform for dialogue with the general public through various science communication activities such as lecture series, visitor programmes and the dissemination of scientific achievements.
Original article: http://www.embl.de/aboutus/communication_outreach/media_relations/
2013/130228_Heidelberg2/PR_Spitz_DNAs_twisted_communication.pdf
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