Perhaps it is something like the real-estate business. What three things make a difference for selling a house? Location, location and location. Thus it may be for at least some of the crucial genes involved in the development of the human embryo. Specifically, researchers at the European Molecular Biology Laboratory (Heidelberg, Germany) found that the crucial developmental gene Fgf8 is effective not because of the gene itself, but because of its location in the genome. As the study leader, Francois Spitz put it,
“We showed that the surprisingly complex organization of this genomic region is a key aspect of the regulation of Fgf8. It 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.”
[Source: DNA’s twisted communication]
This research is part of a massive effort to understand the molecular, biochemical foundations of development, how, for example, the human embryo grows from a single cell into the complex organic being we call a baby. It’s also part of an eye-opening era in biology where the role and context of DNA continues to find greater complexity and, at times, controversy.
In this case, the researchers were looking at a very specific gene, Fgf8, which (apparently) controls the growth of the limbs and formation of various regions in the brain. The sequence of development involved with this gene is extremely complicated (anything involving the brain is complicated) yet everything must happen in sequence with utmost precision. The demands of this process have made the particular area of the genome where Fgf8 is located one of the most stable and ubiquitous among mammals.
By selectively changing the relative positioning of the regulatory elements surrounding Fgf8, the researchers changed the impact of the gene and drastically affected the development of the embryo. It seems likely that the way DNA folds – as guided by histones and other regulatory mechanisms – determines the sequence of development by triggering or preventing gene expression. Their results are published in the journal Developmental Cell [28 February 2013, paywalled, An Integrated Holo-Enhancer Unit Defines Tissue and Gene Specificity of the Fgf8 Regulatory Landscape]
This research is part of a larger path of discovery showing that positioning of genes – what is exposed and what isn’t – may be at least as important as the instructions coded in the genes. What those regulatory mechanisms are, what guides the folding of the DNA for example, are probably crucial to understanding how development occurs.
For some background on DNA folding: [SciTechStory: Histones: DNA packaging and much more]
