A map of regulatory DNA sequences

Along the way, researchers have confirmed the well-known theory that disease-causing mutations often do not come to the genes themselves, but in sequence, regulating their activity.

When we talk about the genes that usually mean a DNA sequence encoding a protein. Here the insulin gene, that gene collagen gene’s some protease (enzyme that breaks down other proteins), etc. However, we all - multicellular creatures, and our “many cells” sometimes dramatically different: compare neuron with intestinal epithelial cells and feel the difference. But in every cell of our genes are the same. But genes are largely determine the structure and function of the cell … In general, it is clear that different genes in different cells work differently. Also, do not forget that the cell itself has been very intense way of development, and for the life activity of its genes changed again.

So we come to the idea of ​​the existence of regulators, switches, switches and switches that change the activity of genes within a cell’s life, depending on the specialization and the current environmental conditions. Indeed, such a regulatory apparatus exists, and it is truly vast. And gene regulation relies heavily on specific sequences in the DNA itself, which do not carry information about proteins, but they are signals for specific proteins, koi, interacted with DNA regulatory element, strengthen or weaken a gene. Such DNA sequences are, for example, promoters, without which transcription can hardly begin and enhancers that may be located quite far from the controlled gene, but nevertheless exert a strong influence on him.

All this is a long preface we need to fully feel the value of the work performed by an international research consortium FANTOM (Functional Annotation of the Mammalian genome), led by Japanese scientists from the Institute of RIKEN. The essence of their results can be expressed in a short phrase, the researchers were able to construct a nearly complete map of regulatory DNA elements of the human genome.

Here are some related numbers: FANTOM project began in 2000, it included more than 250 professionals, mainly in cell biology and bioinformatics, representing 114 research centers in more than 20 countries. Regulatory sequences are searched with the help of the cap-analysis gene expression (CAGE), developed at RIKEN. Without going into the details of this method, we can only say that it just allows you to “catch” the sequences that regulate transcription, and even works with not too active in this sense genes. Furthermore, CAGE allows to deal with not very high initial number of cells.

They worked with an enormous number of cells, both human and mouse. Result: 180 000 described promoter sequences and 44 000 enhancer sequences. All this mass of data has fallen to scientific journals, according to a study …

28 March 2014

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