Involvement of DNA curvature in intergenic regions of prokaryotes

It is known that DNA curvature plays a certain role in gene regulation. The distribution of curved DNA in promoter regions is evolutionarily preserved, and it is mainly determined by temperature of habitat. However, very little is known on the distribution of DNA curvature in termination sites. Our main objective was to comprehensively analyze distribution of curved sequences upstream and downstream to the coding genes in prokaryotic genomes. We applied CURVATURE software to 170 complete prokaryotic genomes in a search for possible typical distribution of DNA curvature around starts and ends of genes. Performing cluster analyses and other statistical tests, we obtained novel results regarding various factors influencing curvature distribution in intergenic regions, such as growth temperature, A+T composition and genome size. We also analyzed intergenic regions between converging genes in 15 selected genomes. The results show that six genomes presented peaks of curvature excess larger than 3 SDs. Insufficient statistics did not allow us to draw further conclusion. Our hypothesis is that DNA curvature could affect transcription termination in many prokaryotes either directly, through contacts with RNA polymerase, or indirectly, via contacts with some regulatory proteins

Sequence periodicity of Escherichia coli is concentrated in intergenic regions

BACKGROUND: Sequence periodicity with a period close to the DNA helical repeat is a very basic genomic property. This genomic feature was demonstrated for many prokaryotic genomes. The Escherichia coli sequences display the period close to 11 base pairs. RESULTS: Here we demonstrate that practically only ApA/TpT dinucleotides contribute to overall dinucleotide periodicity in Escherichia coli. The noncoding sequences reveal this periodicity much more prominently compared to protein-coding sequences. The sequence periodicity of ApC/GpT, ApT and GpC dinucleotides along the Escherichia coli K-12 is found to be located as well mainly within the intergenic regions. CONCLUSIONS: The observed concentration of the dinucleotide sequence periodicity in the intergenic regions of E. coli suggests that the periodicity is a typical property of prokaryotic intergenic regions. We suppose that this preferential distribution of dinucleotide periodicity serves many biological functions; first of all, the regulation of transcription

Portion of predicted nucleosomes by two {AA, TT} and {GG, CC} patterns of human nucleosome and HMM [21].

<p>Portion of predicted nucleosomes by two {AA, TT} and {GG, CC} patterns of human nucleosome and HMM <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003760#pcbi.1003760-Xi1" target="_blank">[21]</a>.</p

Dinucleotide distributions of (A) AA-TT and (B) GG-CC dinucleotides, (C) WW (adenine or thymine), and (D) SS (guanine or cytosine) around nucleosome dyad symmetry, whole sets.

<p>Apoptotic lymphocytes, data is from <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003760#pcbi.1003760-Bettecken1" target="_blank">[14]</a>; CD4⁺ cells, data is from <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003760#pcbi.1003760-Schones1" target="_blank">[8]</a>.</p

Dinucleotide distribution of +1 nucleosome. Group 1 (top panels) of apoptotic [14] + 1 nucleosomes has higher AT/GC ratio than set of normal CD4⁺ cells [8].

<p>Set of CD4⁺ has phased AA, TT dinucleotides and AA-TT peak at the center of nucleosome. Group 2 is at the bottom panel. +1 nucleosome of CD4+ cells has counter phased GG and CC dinucleotide.</p

Apoptotic Lymphocytes of <i>H. sapiens</i> Lose Nucleosomes in GC-Rich Promoters

<div><p>We analyzed two sets of human CD4⁺ nucleosomal DNA directly sequenced by Illumina (Solexa) high throughput sequencing method. The first set has ∼40 M sequences and was produced from the normal CD4+ T lymphocytes by micrococcal nuclease. The second set has ∼44 M sequences and was obtained from peripheral blood lymphocytes by apoptotic nucleases. The different nucleosome sets showed similar dinucleotide positioning AA/TT, GG/CC, and RR/YY (R is purine, Y - pyrimidine) patterns with periods of 10–10.4 bp. Peaks of GG/CC and AA/TT patterns were shifted by 5 bp from each other. Two types of promoters in <i>H. sapiens</i>: AT and GC-rich were identified. AT-rich promoters in apoptotic cell had +1 nucleosome shifts 50–60 bp downstream from those in normal lymphocytes. GC-rich promoters in apoptotic cells lost 80% of nucleosomes around transcription start sites as well as in total DNA. Nucleosome positioning was predicted by combination of {AA, TT}, {GG, CC}, {WW, SS} and {RR, YY} patterns. In our study we found that the combinations of {AA, TT} and {GG, CC} provide the best results and successfully mapped 33% of nucleosomes 147 bp long with precision ±15 bp (only 31/147 or 21% is expected).</p></div

Apoptotic Lymphocytes of <i>H. sapiens - Figure 1 </i> Lose Nucleosomes in GC-Rich Promoters

<p>(<b>A</b>) <b>Distribution of nucleosomes around transcription start sites; blue line corresponds to apoptotic lymphocytes <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003760#pcbi.1003760-Bettecken1" target="_blank">[14]</a>; black line corresponds to normal CD4⁺ cells <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003760#pcbi.1003760-Schones1" target="_blank">[8]</a>.</b> (<b>B</b>) Distribution of nucleosomes around transcription start sites; 32,038 promoters were divided into two groups by nucleosome occupancy in apoptotic lymphocytes <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003760#pcbi.1003760-Bettecken1" target="_blank">[14]</a>, K-means clustering method: blue line corresponds to the first group of 16670 promoters with normal occurrence (one nucleosome per 250 bp) of nucleosomes; black line corresponds to the second group of 15368 promoters with low occurrence (one nucleosome per 1000 bp) of nucleosomes around TSS. (<b>C</b>) Distribution of nucleosomes around transcription start sites. Blue and red lines correspond to promoters of the first group with normal occupancy of nucleosomes, apoptotic lymphocytes and CD4⁺ cells respectively. These promoters have the similar average occupancy of nucleosomes, position of +1 nucleosome from set of apoptotic lymphocytes <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003760#pcbi.1003760-Bettecken1" target="_blank">[14]</a> is shifted 50–60 bp downstream. Black and orange lines correspond to promoters with low occupancy of nucleosomes during apoptosis, apoptotic lymphocytes and normal CD4+ cells respectively. These promoters lost 80% of nucleosomes around TSS during apoptosis.</p

Nucleosome occurrence per promoter (±1000 bp around TSS).

<p>Nucleosome occurrence per promoter (±1000 bp around TSS).</p

Nucleosome positioning sequence patterns as packing or regulatory

Nucleosome 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”)

Galaxy Dnpatterntools for Computational Analysis of Nucleosome Positioning Sequence Patterns

Nucleosomes are basic units of DNA packing in eukaryotes. Their structure is well conserved from yeast to human and consists of the histone octamer core and 147 bp DNA wrapped around it. Nucleosomes are bound to a majority of the eukaryotic genomic DNA, including its regulatory regions. Hence, they also play a major role in gene regulation. For the latter, their precise positioning on DNA is essential. In the present paper, we describe Galaxy dnpatterntools&mdash;software package for nucleosome DNA sequence analysis and mapping. This software will be useful for computational biologists practitioners to conduct more profound studies of gene regulatory mechanisms