A. KeльПодвижность регуляторного кода. Эволюционные и медицинские последствия
Четверг, 9 декабря 2010, 18.00
Институт молекулярной биологии (Вавилова, 32), к. 309.
geneXplain GmbH, Wolfenbuttel, Germany
Flexibility of regulatory code. Application in evolution and diseases
The multiplicity of cellular conditions for eukaryotic genes to be expressed gives rise to the polyfunctionality of the structure of their transcription regulatory regions. I propose a "fuzzy puzzle" hypothesis of organization of transcription regulatory code, which allows to encode multiple regulatory messages in the same DNA sequence in the regulatory regions of eukaryotic genes. The structure of regulatory sequences on one hand and the specific features of transcription factors on the other hand provide a possibility to encode several regulatory programs within one regulatory region. It is known that each transcription factor has the ability to bind to a variety of different DNA sites. This is maintained by flexible mechanisms of DNA-protein interactions, when DNA conformation rather than the particular sequence context often plays the major role in selection of DNA targets. In addition, the ability of TFs to operate through a so-called "induced fit" mechanism (when a TF becomes finally structured only upo
n interaction with DNA; Frankel and Kim, 1991) greatly relaxes the restrictions from binding to various DNA sites. Besides that, the protein-protein interactions between different transcription factors in the multiprotein regulatory complexes can stabilize low-energy protein-DNA contacts thus additionally widen the variety of target sites for particular transcription factors. The huge diversity of transcription factors functioning in the living cells multiplied by the wide choice of target sites for each TF gives rise to a precondition to form multiple alternative DNA-protein complexes on the same gene regulatory region. As a result extremely complex patterns of gene expression are observed.I will discuss how, I think, the "fuzzy puzzle" breaks off the evolutional limitations on multicellular organization and how it becomes the basis for a new, very effective mechanism of evolution. I also will discuss the application of the "fuzzy puzzle" hypothesis in understanding mechanisms of complex diseases and possibl
e ways how to battle them.