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Archive - Feb 28, 2013

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Genome Architecture and Gene Regulation

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 the European Molecular Biology Laboratory (EMBL) have elucidated how Fgf8 in mammal embryos is, itself, controlled by a series of multiple, interdependent regulatory elements. Their findings, published online on February 28, 2013 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, the researchers were able to modify their combined impact on Fgf8, and therefore drastically affect the embryo. “We showed that the surprisingly complex organization of this genomic region is a key aspect of the regulation of Fgf8,” explains Dr. 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 regulatory mechanism.

First Results of Human Microbiome Project Reported

Earth Day may be more than a month away, but another, more personal, ecosystem has been shown to also be worth protecting—within our bodies are communities of microbes that affect the behavior of human cells hosting them. These communities, called the "microbiome," are so crucial to our health that some consider it to be a complex "second genome." Understanding the interaction of these microbes among one another and their human hosts has the potential to yield insights into numerous diseases and complex human disorders from obesity to susceptibility to infection. In a new report appearing in the March 2013 issue of The FASEB Journal, scientists take an important step toward designing a uniform protocol for microbiome research that ensures proper controls and considerations for variations among people. By doing this, future researchers should be able to better assess how what we ingest, whether drugs or food, affects our bodies. "While historically pre- and probiotics have dominated the microbiome landscape, emerging data from numerous labs as to the impact of dietary interventions and antibiotic exposure will play formative roles in tailoring therapy," said Kjersti M. Aagaard, M.D., Ph.D., from the Department of Obstetrics and Gynecology at Baylor College of Medicine in Houston, Texas. "We may find that the answers to our most common and prevalent health and disease states lie not in manipulating the human genome, but rather, in utilizing subtle shifts in diet and components of the diet, efficacy trials in prophylactic or preventative antibiotic therapies, and careful attention to the over prescription of steroids and antibiotics." Dr. Aagaard and colleagues completed comprehensive body site sampling in healthy 18-40 year old adults, creating an unparalleled reference set of microbiome specimens.