The Chromatin Organization of an Eukaryotic Genome : Sequence Specific+ Statistical=Combinatorial (Extended Abstract)

Nucleosome organization in eukaryotic genomes has a deep impact on gene function. Although progress has been recently made in the identification of various concurring factors influencing nucleosome positioning, it is still unclear whether nucleosome positions are sequence dictated or determined by a random process. It has been postulated for a long time that, in the proximity of TSS, a barrier determines the position of the +1 nucleosome and then geometric constraints alter the random positioning process determining nucleosomal phasing. Such a pattern fades out as one moves away from the barrier to become again a random positioning process. Although this statistical model is widely accepted, the molecular nature of the barrier is still unknown. Moreover, we are far from the identification of a set of sequence rules able: to account for the genome-wide nucleosome organization; to explain the nature of the barriers on which the statistical mechanism hinges; to allow for a smooth transition from sequence-dictated to statistical positioning and back. Here we show that sequence complexity, quantified via various methods, can be the rule able to at least partially account for all the above. In particular, we have conducted our analyses on four high resolution nucleosomal maps of the model eukaryotes S.cerevisiae, C. elegans and D.melanogaster, and found that nucleosome depleted regions can be well distinguished from nucleosome enriched regions by sequence complexity measures. In particular, the depleted regions are less complex than the enriched ones. Moreover, around TSS, complexity measures alone are in striking agreement with in vivo nucleosome occupancy, in particular precisely indicating the positions of the +1 and -1 nucleosomes. Those findings indicate that the intrinsic richness of subsequences within sequences plays a role in nucleosomal formation in genomes, and that sequence complexity constitutes the molecular nature of nucleosome barrier.