Nucleosome positioning sequence patterns as packing or regulatory

Abstract

AbstractNucleosome positioning DNA sequence patterns (NPS) - usually distributions of particular dinucleotides or other sequence elements in nucleosomal DNA - at least partially determine chromatin structure and arrangements of nucleosomes that in turn affect gene expression. Statistically, NPS are defined as oscillations of the dinucleotide periodicity with about 10 base pairs (bp) which reflects the double helix period. We compared the nucleosomal DNA patterns in mouse, human and yeast organisms and observed few distinctive patterns that can be termed as packing and regulatory referring to distinctive modes of chromatin function. For the first time the NPS patterns in nucleus accumbens cells (NAC) in mouse brain were characterized and compared to the patterns in human CD4+ and apoptotic lymphocyte cells and well studied patterns in yeast. The NPS patterns in human CD4+ cells and mouse brain cells had very high positive correlation. However, there was no correlation between them and patterns in human apoptotic lymphocyte cells and yeast, but the latter two were highly correlated with each other. By their dinucleotide arrangements the analyzed NPS patterns classified into stable canonical WW/SS (W=A or T and S=C or G dinucleotide) and less stable RR/YY (R=A or G and Y =C or T dinucleotide) patterns and anti-patterns In the anti-patterns positioning of the dinucleotides is flipped compared to those in the regular patterns. Stable canonical WW/SS patterns and anti-patterns are ubiquitously observed in many organisms and they had high resemblance between yeast and human apoptotic cells. Less stable RR/YY patterns had higher positive correlation between mouse and normal human cells. Our analysis and evidence from scientific literature lead to idea that various distinct patterns in nucleosomal DNA can be related to the two roles of the chromatin: packing (WW/SS) and regulatory (RR/YY and “anti”).Author summaryPrecise positioning of nucleosomes on DNA sequence is essential for gene regulatory processes. Two main classes of nucleosome positioning sequence (NPS) patterns with a periodicity of 10bp for their sequence elements were previously described. In the 1st class AA,TT and other WW dinucleotides (W= A or T) tend to occur together in the major groove of DNA closest to the histone octamer, while SS dinucleotides (S= G or C) are primarily positioned in the major groove facing outward. In the 2nd class AA and TT are structurally separated (AA backbone near the histone octamer, and TT backbone further away), but grouped with other RR (R is purine A or G) and YY (Y is pyrimidine C or T) dinucleotides. In [8] we also described novel anti-NPS patterns, inverse to the conventional NPS patterns: WW runs inverse to SS, RR inverse to YY. We demonstrated that Yeast nucleosomes in promoters show higher correlation to the RR/YY pattern whereas novel anti-NPS patterns are viable for nucleosomes in the promoters of stress associated genes related to active chromatin remodeling. In the present study we attribute different functions to various NPS patterns: packing function to WW/SS and regulatory – to RR/YY and anti-NPS patterns.