Abstract

BackgroundThe periodical occurrence of dinucleotides with a period of 10.4 bases now is undeniably a hallmark of nucleosome positioning. Whereas many eukaryotic genomes contain visible and even strong signals for periodic distribution of dinucleotides, the human genome is rather featureless in this respect. The exact sequence features in the human genome that govern the nucleosome positioning remain largely unknown.ResultsWhen analyzing the human genome sequence with the positional autocorrelation method, we found that only the dinucleotide CG shows the 10.4 base periodicity, which is indicative of the presence of nucleosomes. There is a high occurrence of CG dinucleotides that are either 31 (10.4 × 3) or 62 (10.4 × 6) base pairs apart from one another - a sequence bias known to be characteristic of Alu-sequences. In a similar analysis with repetitive sequences removed, peaks of repeating CG motifs can be seen at positions 10, 21 and 31, the nearest integers of multiples of 10.4.ConclusionsAlthough the CG dinucleotides are dominant, other elements of the standard nucleosome positioning pattern are present in the human genome as well.The positional autocorrelation analysis of the human genome demonstrates that the CG dinucleotide is, indeed, one visible element of the human nucleosome positioning pattern, which appears both in Alu sequences and in sequences without repeats. The dominant role that CG dinucleotides play in organizing human chromatin is to indicate the involvement of human nucleosomes in tuning the regulation of gene expression and chromatin structure, which is very likely due to cytosine-methylation/-demethylation in CG dinucleotides contained in the human nucleosomes. This is further confirmed by the positions of CG-periodical nucleosomes on Alu sequences. Alu repeats appear as monomers, dimers and trimers, harboring two to six nucleosomes in a run. Considering the exceptional role CG dinucleotides play in the nucleosome positioning, we hypothesize that Alu-nucleosomes, especially, those that form tightly positioned runs, could serve as "anchors" in organizing the chromatin in human cells.

Highlights

  • The periodical occurrence of dinucleotides with a period of 10.4 bases now is undeniably a hallmark of nucleosome positioning

  • The CG-containing Alu-sequences and periodical CG dinucleotides in the non-repetitive bulk of human DNA seem to be the only signatures of nucleosome positioning in the human genome (Figures 1 and 2), which can be revealed by the positional autocorrelation analysis

  • The preferential use of CG dinucleotides in human chromatin is the illustration

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Summary

Introduction

The periodical occurrence of dinucleotides with a period of 10.4 bases now is undeniably a hallmark of nucleosome positioning. Whereas many eukaryotic genomes contain visible and even strong signals for periodic distribution of dinucleotides, the human genome is rather featureless in this respect. The periodical distribution of various dinucleotides along eukaryotic DNA sequences with a period of 10-11 bases is commonly considered as the manifestation of a nucleosome positioning signal present in the sequences [1,2,3,4,5,6,7,8]. The period, the more accurate value of which is 10.4 bases [9,10,11,12], corresponds to the helical repeat of DNA in the nucleosome. The positioning signal in human nucleosomes is rather weak and lacks the periodical AA and TT dinucleotides [13], while in yeast and nematodes the periodical nucleosome signals are

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