title: The human genomic melting map.
abstract: 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.
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Eivind
authors.initials: E
authors.lastname: Tøstesen
authors.forename: Jostein K
authors.initials: JK
authors.lastname: Sundet
authors.forename: Tor-Kristian
authors.initials: TK
authors.lastname: Jenssen
authors.forename: Christoph
authors.initials: C
authors.lastname: Bock
authors.forename: Geir Ivar
authors.initials: GI
authors.lastname: Jerstad
authors.forename: William G
authors.initials: WG
authors.lastname: Thilly
authors.forename: Eivind
authors.initials: E
authors.lastname: Hovig
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D017422:Sequence Analysis, DNA / Q000379:methods*; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D004247:DNA