The human genomic melting map.

In a living cell, the antiparallel double-stranded helix of DNA is a dynamically changing structure. The structure relates to interactions between and within the DNA strands, and the array of other macromolecules that constitutes functional chromatin. It is only through its changing conformations that DNA can organize and structure a large number of cellular functions. In particular, DNA must locally uncoil, or melt, and become single-stranded for DNA replication, repair, recombination, and transcription to occur. It has previously been shown that this melting occurs cooperatively, whereby several base pairs act in concert to generate melting bubbles, and in this way constitute a domain that behaves as a unit with respect to local DNA single-strandedness. We have applied a melting map calculation to the complete human genome, which provides information about the propensities of forming local bubbles determined from the whole sequence, and present a first report on its basic features, the extent of cooperativity, and correlations to various physical and biological features of the human genome. Globally, the melting map covaries very strongly with GC content. Most importantly, however, cooperativity of DNA denaturation causes this correlation to be weaker at resolutions fewer than 500 bps. This is also the resolution level at which most structural and biological processes occur, signifying the importance of the informational content inherent in the genomic melting map. The human DNA melting map may be further explored at http://meltmap.uio.no.

Stitchprofiles.uio.no: analysis of partly melted DNA conformations using stitch profiles.

In this study, we describe a web server that performs computations on DNA melting, thus predicting the localized separation of the two strands for sequences provided by the users. The output types are stitch profiles, melting curves, probability profiles, etc. Stitch profile diagrams visualize the ensemble of alternative conformations that DNA can adopt with different probabilities. For example, a stitch profile shows the possible loop openings in terms of their locations, sizes, probabilities and fluctuations at a given temperature. Sequences with lengths up to several tens or hundreds of kilobase pairs can be analysed. The tools are freely available at http://stitchprofiles.uio.no.