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The spatial organization principles of eukaryotic genome remain unclear. Current hypotheses range from the idea of hierarchical folding to the "polymer melt" model. Great amount of data about chromatin structure was obtained using electron microscopy. Although it allows for high resolution, it has several disadvantages over light microscopy, long multistep sample preparation that casts doubts on structure nativity being one of them. Chromatin is a very heterogeneous structure and it is sensitive to the experimental conditions. This requires development of sample preparation approaches combining good structure preservation with efficient selective labeling of structural-functional chromatin states. Here we used a modified method of replicative labeling (1) adapted for strong aldehyde fixation and validated it using CLEM (STORM, TEM).