Nucleosome positioning sequence patterns as packing or regulatory

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.

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Nucleosome Positioning with Set of Key Positions and Nucleosome Affinity

The Open Biomedical Engineering Journal ◽

10.2174/1874120701408010166 ◽

2014 ◽

Vol 8 (1) ◽

pp. 166-170 ◽

Cited By ~ 1

Author(s):

Jia Wang ◽

Shuai Liu ◽

Weina Fu

Keyword(s):

Neural Network ◽

Experimental Data ◽

Dna Sequence ◽

Dna Sequences ◽

Nucleosome Positioning ◽

Experimental Results ◽

Negative Effects ◽

Sequence Structure ◽

Precise Positioning ◽

Histone Octamer

The formation and precise positioning of nucleosome in chromatin occupies a very important role in studying life process. Today, there are many researchers who discovered that the positioning where the location of a DNA sequence fragment wraps around a histone octamer in genome is not random but regular. However, the positioning is closely relevant to the concrete sequence of core DNA. So in this paper, we analyzed the relation between the affinity and sequence structure of core DNA, and extracted the set of key positions. In these positions, the nucleotide sequences probably occupy mainly action in the binding. First, we simplified and formatted the experimental data with the affinity. Then, to find the key positions in the wrapping, we used neural network to analyze the positive and negative effects of nucleosome generation for each position in core DNA sequences. However, we reached a class of weights with every position to describe this effect. Finally, based on the positions with high weights, we analyzed the reason why the chosen positions are key positions, and used these positions to construct a model for nucleosome positioning prediction. Experimental results show the effectiveness of our method.

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Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations

10.1101/177436 ◽

2017 ◽

Author(s):

Toru Niina ◽

Giovanni B. Brandani ◽

Cheng Tan ◽

Shoji Takada

Keyword(s):

Hydrogen Bond ◽

Dna Sequence ◽

Base Pair ◽

Sliding Mode ◽

Nucleosome Positioning ◽

Eukaryotic Genome ◽

Coarse Grained ◽

Histone Octamer ◽

Hydrogen Bond Interactions ◽

Nucleosome Sliding

AbstractWhile nucleosome positioning on eukaryotic genome play important roles for genetic regulation, molecular mechanisms of nucleosome positioning and sliding along DNA are not well understood. Here we investigated thermally-activated spontaneous nucleosome sliding mechanisms developing and applying a coarse-grained molecular simulation method that incorporates both long-range electrostatic and short-range hydrogen-bond interactions between histone octamer and DNA. The simulations revealed two distinct sliding modes depending on the nucleosomal DNA sequence. A uniform DNA sequence showed frequent sliding with one base pair step in a rotation-coupled manner, akin to screw-like motions. On the contrary, a strong positioning sequence, the so-called 601 sequence, exhibits rare, abrupt transitions of five and ten base pair steps without rotation. Moreover, we evaluated the importance of hydrogen bond interactions on the sliding mode, finding that strong and weak bonds favor respectively the rotation-coupled and -uncoupled sliding movements.Author summaryNucleosomes are fundamental units of chromatin folding consisting of double-stranded DNA wrapped ∼1.7 times around a histone octamer. By densely populating the eukaryotic genome, nucleosomes enable efficient genome compaction inside the cellular nucleus. However, the portion of DNA occupied by a nucleosome can hardly be accessed by other DNA-binding proteins, obstructing fundamental cellular processes such as DNA replication and transcription. DNA compaction and access by other proteins can simultaneously be achieved via the dynamical repositioning of nucleosomes, which can slide along the DNA sequence. In this study, we developed and used coarse-grained molecular dynamics simulations to reveal the molecular details of nucleosome sliding. We find that the sliding mode is highly dependent on the underlying DNA sequence. Specifically, a sequence with a strong nucleosome positioning signal slides via large jumps by five and ten base pairs, preserving the optimal DNA bending profile. On the other hand, uniform sequences without the positioning signal slide via a screw-like motion of DNA, one base pair at the time. These results show that sequence has a large effect not only on the formation of nucleosomes, but also on the kinetics of repositioning.

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