PubGene (Norway)

The accurate prediction and characterization of DNA melting domains by computationaltools could facilitate a broad range of biological applications. However, no algorithm formelting domain prediction has been available until now. The main challenges include thedifficulty of mathematically mapping a qualitative description of DNA melting domains toquantitative statistical mechanics models, as well as the absence of ‘gold standards’ and aneed for generality. In this paper, we introduce a new approach to identify the twostateregions and melting fork regions along a given DNA sequence. Compared with an ad hocsegmentation used in one of our previous studies, the new algorithm is based on boundaryprobability profiles, rather than standard melting maps. We demonstrate that a moredetailed characterization of the DNA melting domain map can be obtained using our newmethod, and this approach is independent of the choice of DNA melting model. Weexpect this work to drive our understanding of DNA melting domains one stepfurther.

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.