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1.
Edward N. Trifonov 《Journal of biomolecular structure & dynamics》2016,34(4):724-731
Lowary and Widom selected from random sequences those which form exceptionally stable nucleosomes, including clone 601, the current champion of strong nucleosome (SN) sequences. This unique sequence database (LW sequences) carries sequence elements which confer stability on the nucleosomes formed on the sequences, and, thus, may serve as source of information on the structure of “ideal” or close to ideal nucleosome DNA sequence. An important clue is also provided by crystallographic study of Vasudevan and coauthors on clone 601 nucleosomes. It demonstrated that YR·YR dinucleotide stacks (primarily TA·TA) follow one another at distances 10 or 11 bases or multiples thereof, such that they all are located on the interface between DNA and histone octamer. Combining this important information with alignment of the YR-containing 10-mers and 11-mers from LW sequences, the bendability matrices of the stable nucleosome DNA are derived. The matrices suggest that the periodically repeated TA (YR), RR, and YY dinucleotides are the main sequence features of the SNs. This consensus coincides with the one for recently discovered SNs with visibly periodic DNA sequences. Thus, the experimentally observed stable LW nucleosomes and SNs derived computationally appear to represent the same entity – exceptionally stable SNs. 相似文献
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I. Gabdank D. Barash E. N. Trifonov 《Journal of biomolecular structure & dynamics》2013,31(4):403-411
Abstract An original signal extraction procedure is applied to database of 146 base nucleosome core DNA sequences from C. elegans (S. M. Johnson et al. Genome Research 16, 1505–1516, 2006). The positional preferences of various dinucleotides within the 10.4 base nucleosome DNA repeat are calculated, resulting in derivation of the nucleosome DNA bendability matrix of 16x10 elements. A simplified one-line presentation of the matrix (“consensus” repeat) is…A(TTTCCGGAAA)T…. All 6 chromosomes of C. elegans conform to the bendability pattern. The strongest affinity to their respective positions is displayed by dinucleotides AT and CG, separated within the repeat by 5 bases. The derived pattern makes a basis for sequence-directed mapping of nucleosome positions in the genome of C. elegans. As the first complete matrix of bendability available the pattern may serve for iterative calculations of the species-specific matrices of bendability applicable to other genomic sequences. 相似文献
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Abstract By measuring prevailing distances between YY, YR, RR, and RY dinucleotides in the large database of the nucleosome DNA fragments from C. elegans, the consensus sequence structure of the nucleosome DNA repeat of C. elegans was reconstructed: (YYYYYRRRRR)n. An actual period was estimated to be 10.4 bases. The pattern is fully consistent with the nucleosome DNA patterns of other eukaryotes, as established earlier, and, thus, the YYYYYRRRRR repeat can be considered as consensus nucleosome DNA sequence repeat across eukaryotic species. Similar distance analysis for [A, T] dinucleotides suggested the related pattern (TTTYTARAAA)n where the TT and AA dinucleotides display rather out of phase behavior, contrary to the “AA or TT” in-phase periodicity, considered in some publications. A weak 5-base periodicity in the distribution of TA dinucleotides was detected. 相似文献
4.
Edward N. Trifonov 《Journal of biomolecular structure & dynamics》2013,31(6):741-746
Abstract All major suggestions about the nucleosome positioning sequence pattern(s) are overviewed. Two basic binary periodical patterns are well established: in purine/pyrimidine alphabet—YRRRRRYYYYYR and in strong/weak alphabet-SWWWWWSSSSSW. Their merger in four-letter alphabet sequence coincides with first ever complete matrix of nucleosome DNA bendability derived from very large database of nucleosome DNA sequences. Its simplified linear form is CGGAAATTTCCG. Several independent ways of derivation of the same pattern are described. It appears that the pattern represents an ultimate solution of long-standing problem of nucleosome positioning, and provides simple means for nucleosome mapping on sequences with single-base resolution. 相似文献
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The bulk of strong nucleosomes (SNs, with visibly periodic DNA sequences) is described by consensus pattern of 5 or 6 base runs of purines alternating with similar runs of pyrimidines – RR/YY SNs. Yet, the strongest known nucleosome positioning sequence, the 601 clone of Lowary and Widom, is rather periodic repetition of TA dinucleotides following one another every 10 bases. We located “601”-like TA-periodic sequences in the genome of A. thaliana. Several families of such sequences are discovered repeating almost exclusively in centromeres. Thus, while A. thaliana SNs of RR/YY type have strong affinity to pericentromeric regions, as it has been previously found, the SNs of TA periodic type concentrate rather in centromeres. 相似文献
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Unmethylated and methylated CpG dinucleotides distinctively regulate the physical properties of DNA
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In eukaryotic cells, DNA has to bend significantly to pack inside the nucleus. Physical properties of DNA such as bending flexibility and curvature are expected to affect DNA packaging and partially determine the nucleosome positioning patterns inside a cell. DNA CpG methylation, the most common epigenetic modification found in DNA, is known to affect the physical properties of DNA. However, its detailed role in nucleosome formation is less well‐established. In this study, we evaluated the effect of defined CpG patterns (unmethylated and methylated) on DNA structure and their respective nucleosome‐forming ability. Our results suggest that the addition of CpG dinucleotides, either as a (CG)n stretch or (CGX8)n repeats at 10 bp intervals, lead to reduced hydrodynamic radius and decreased nucleosome‐forming ability of DNA. This effect is more predominant for a DNA stretch ((CG)5) located in the middle of a DNA fragment. Methylation of CpG sites, surprisingly, seems to reduce the difference in DNA structure and nucleosome‐forming ability among DNA constructs with different CpG patterns. Our results suggest that unmethylated and methylated CpG patterns can play very different roles in regulating the physical properties of DNA. CpG methylation seems to reduce the DNA conformational variations affiliated with defined CpG patterns. Our results can have significant bearings in understanding the nucleosome positioning pattern in living organisms modulated by DNA sequences and epigenetic features. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 517–524, 2014. 相似文献
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Positional distributions of various dinucleotides in experimentally derived human nucleosome DNA sequences are analyzed. Nucleosome positioning in this species is found to depend largely on GG and CC dinucleotides periodically distributed along the nucleosome DNA sequence, with the period of 10.4 bases. The GG and CC dinucleotides oscillate counterphase, i.e., their respective preferred positions are shifted about a half-period from one another, as it was observed earlier for AA and TT dinucleotides. Other purine-purine and pyrimidine-pyrimidine dinucleotides (RR and YY) display the same periodical and counterphase pattern. The dominance of oscillating GG and CC dinucleotides in human nucleosomes and the contribution of AG(CT), GA(TC), and AA(TT) suggest a general nucleosome DNA sequence pattern - counterphase oscillation of RR and YY dinucleotides. AA and TT dinucleotides, commonly accepted as major players, are only weak contributors in the case of human nucleosomes. 相似文献
10.
Kato M Onishi Y Wada-Kiyama Y Abe T Ikemura T Kogan S Bolshoy A Trifonov EN Kiyama R 《Journal of molecular biology》2003,332(1):111-125
Dinucleosome formation is the first step in the organization of the higher order chromatin structure. With the ultimate aim of elucidating the dinucleosome structure, we constructed a library of human dinucleosome DNA. The library consists of PCR-amplifiable DNA fragments obtained by treatment of nuclei of erythroid K562 cells with micrococcal nuclease followed by extraction of DNA and adaptor ligation to the blunt-ended DNA fragments. The library was then cloned using a plasmid vector and the sequences of the clones were determined. The dominating clones containing the Alu elements were removed. A total of 1002 clones, which comprised a dinucleosome database, contained 84 and 918 clones from the clones before and after removing Alu elements, respectively. Approximately 70% of the clones were between 300 and 400 bp in size and they were distributed to various locations of all chromosomes except the Y chromosome. The clones containing A(2)N(8)A(2)N(8)A(2) or T(2)N(8)T(2)N(8)T(2) sequences were classified into three types, Type I (N shape), Type II (V shape) and Type III (M shape) according to DNA curvature plots. The locations of experimentally determined curved DNA segments matched well with the calculated ones though the clones of Types I and III showed additional curved DNA segments as revealed by the curvature plots. The distributions of complementary dinucleotides in the nucleosome DNA, at the ends of the dinucleosome DNA clones, allowed us to predict the positions of the nucleosome dyad axis, and estimate the size of the nucleosome core DNA, 125nt. The distributions of AA and TT dinucleotides, as well as other RR and YY dinucleotides, showed a periodicity with an average period of 10.4 bases, close to the values observed before. Mapping of nucleosome positions in the dinucleosome database based on the observed periodicity revealed that the nucleosomes were separated by a linker of 7.5+ approximately 10 x n nt. This indicates that the nucleosome-nucleosome orientations are, typically, halfway between parallel and antiparallel. Also an important finding is that the distributions of AA/TT and other RR/YY dinucleotides, apparently, reflect both DNA curvature and DNA bendability, cooperatively contributing to the nucleosome formation. 相似文献
11.
Walker Hoolehan Justin C Harris Jennifer N Byrum Destiny A Simpson Karla
K Rodgers 《Nucleic acids research》2022,50(20):11696
In the adaptive immune system, V(D)J recombination initiates the production of a diverse antigen receptor repertoire in developing B and T cells. Recombination activating proteins, RAG1 and RAG2 (RAG1/2), catalyze V(D)J recombination by cleaving adjacent to recombination signal sequences (RSSs) that flank antigen receptor gene segments. Previous studies defined the consensus RSS as containing conserved heptamer and nonamer sequences separated by a less conserved 12 or 23 base-pair spacer sequence. However, many RSSs deviate from the consensus sequence. Here, we developed a cell-based, massively parallel assay to evaluate V(D)J recombination activity on thousands of RSSs where the 12-RSS heptamer and adjoining spacer region contained randomized sequences. While the consensus heptamer sequence (CACAGTG) was marginally preferred, V(D)J recombination was highly active on a wide range of non-consensus sequences. Select purine/pyrimidine motifs that may accommodate heptamer unwinding in the RAG1/2 active site were generally preferred. In addition, while different coding flanks and nonamer sequences affected recombination efficiency, the relative dependency on the purine/pyrimidine motifs in the RSS heptamer remained unchanged. Our results suggest RAG1/2 specificity for RSS heptamers is primarily dictated by DNA structural features dependent on purine/pyrimidine pattern, and to a lesser extent, RAG:RSS base-specific interactions. 相似文献
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By measuring prevailing distances between YY, YR, RR, and RY dinucleotides in the large database of the nucleosome DNA fragments from C. elegans, the consensus sequence structure of the nucleosome DNA repeat of C. elegans was reconstructed: (YYYYYRRRRR)n. An actual period was estimated to be 10.4 bases. The pattern is fully consistent with the nucleosome DNA patterns of other eukaryotes, as established earlier, and, thus, the YYYYYRRRRR repeat can be considered as consensus nucleosome DNA sequence repeat across eukaryotic species. Similar distance analysis for [A, T] dinucleotides suggested the related pattern (TTTYTARAAA)n where the TT and AA dinucleotides display rather out of phase behavior, contrary to the "AA or TT" in-phase periodicity, considered in some publications. A weak 5-base periodicity in the distribution of TA dinucleotides was detected. 相似文献
13.
Dileep Vasudevan 《Journal of molecular biology》2010,403(1):1-10
Nucleosome positioning plays a key role in genomic regulation by defining histone-DNA context and by modulating access to specific sites. Moreover, the histone-DNA register influences the double-helix structure, which in turn can affect the association of small molecules and protein factors. Analysis of genomic and synthetic DNA has revealed sequence motifs that direct nucleosome positioning in vitro; thus, establishing the basis for the DNA sequence dependence of positioning would shed light on the mechanics of the double helix and its contribution to chromatin structure in vivo. However, acquisition of well-diffracting nucleosome core particle (NCP) crystals is extremely dependent on the DNA fragment used for assembly, and all previous NCP crystal structures have been based on human α-satellite sequences. Here, we describe the crystal structures of Xenopus NCPs containing one of the strongest known histone octamer binding and positioning sequences, the so-called ‘601’ DNA.Two distinct 145-bp 601 crystal forms display the same histone-DNA register, which coincides with the occurrence of DNA stretching-overtwisting in both halves of the particle around five double-helical turns from the nucleosome center, giving the DNA an ‘effective length’ of 147 bp. As we have found previously with stretching around two turns from the nucleosome center for a centromere-based sequence, the terminal stretching observed in the 601 constructs is associated with extreme kinking into the minor groove at purine-purine (pyrimidine-pyrimidine) dinucleotide steps. In other contexts, these step types display an overall nonflexible behavior, which raises the possibility that DNA stretching in the nucleosome or extreme distortions in general have unique sequence dependency characteristics. Our findings indicate that DNA stretching is an intrinsically predisposed site-specific property of the nucleosome and suggest how NCP crystal structures with diverse DNA sequences can be obtained. 相似文献
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Bilal F. Salih Vladimir B. Teif Vijay Tripathi Edward N. Trifonov 《Journal of biomolecular structure & dynamics》2013,31(6):1164-1175
Recently discovered strong nucleosomes (SNs) characterized by visibly periodical DNA sequences have been found to concentrate in centromeres of Arabidopsis thaliana and in transient meiotic centromeres of Caenorhabditis elegans. To find out whether such affiliation of SNs to centromeres is a more general phenomenon, we studied SNs of the Mus musculus. The publicly available genome sequences of mouse, as well as of practically all other eukaryotes do not include the centromere regions which are difficult to assemble because of a large amount of repeat sequences in the centromeres and pericentromeric regions. We recovered those missing sequences using the data from MNase-seq experiments in mouse embryonic stem cells, where the sequence of DNA inside nucleosomes, including missing regions, was determined by 100-bp paired-end sequencing. Those nucleosome sequences, which are not matching to the published genome sequence, would largely belong to the centromeres. By evaluating SN densities in centromeres and in non-centromeric regions, we conclude that mouse SNs concentrate in the centromeres of telocentric mouse chromosomes, with ~3.9 times excess compared to their density in the rest of the genome. The remaining non-centromeric SNs are harbored mainly by introns and intergenic regions, by retro-transposons, in particular. The centromeric involvement of the SNs opens new horizons for the chromosome and centromere structure studies. 相似文献
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We have mapped in vitro nucleosome positioning on the sheep β-lactoglobulin gene using high-throughput sequencing to characterise the DNA sequences recovered from reconstituted nucleosomes. This methodology surpasses previous approaches for coverage, accuracy and resolution and, most importantly, offers a simple yet rapid and relatively inexpensive method to characterise genomic DNA sequences in terms of nucleosome positioning capacity. We demonstrate an unambiguous correspondence between in vitro and in vivo nucleosome positioning around the promoter of the gene; identify discrete, sequence-specific nucleosomal structures above the level of the canonical core particle—a feature that has implications for regulatory protein access and higher-order chromatin packing; and reveal new insights into the involvement of periodically organised dinucleotide sequence motifs of the type GG and CC and not AA and TT, as determinants of nucleosome positioning—an observation that supports the idea that the core histone octamer can exploit different patterns of sequence organisation, or structural potential, in the DNA to bring about nucleosome positioning. 相似文献
17.
Amir B. Cohanim Yechezkel Kashi Edward N. Trifonov 《Journal of biomolecular structure & dynamics》2013,31(6):687-693
Abstract Positional correlation analysis for the complete genome of Saccharomyces cerevisiae is performed with the aim to reveal possible chromatin-related sequence features. A strong periodicity with the period 10.4 bases is detected in the distance histograms for the dinucleotides AA and TT, with the characteristic decay distance of approximately 50 base pairs. The oscillations are observed as well in the distributions of other dinucleotides. However, the respective amplitudes are small, consistent with secondary effects, due to dominant periodicity of AA and TT. The observations are in accord with earlier data on the chromatin sequence periodicities and nucleosome DNA sequence patterns. The autocorrelations of AA and TT dinucleotides in yeast include also a counter-phase component. A tentative DNA sequence pattern for the yeast nucleosomes is suggested and verified by comparison of its autocorrelation plots with the respective natural autocorrelations. The nucleosome mapping guided by the pattern is in accord with experimental data on the linker length distribution in yeast. 相似文献
18.
Kaifu Chen Lei Wang Meng Yang Jiucheng Liu Chengqi Xin Songnian Hu Jun Yu 《基因组蛋白质组与生物信息学报(英文版)》2010,8(2):92-102
Our recent investigation in the protist Trichomonas vaginalis suggested a DNA sequence periodicity with a unit length of 120.9 nt, which represents a sequence signature for nucleosome positioning. We now extended our observation in higher eukaryotes and identified a similar periodicity of 175 nt in length in Caenorhabditis elegans. In the process of defining the sequence compositional characteristics, we found that the 10.5-nt periodicity, the sequence signature of DNA double helix, may not be sufficient for cross-nucleosome positioning but provides essential guiding rails to facilitate positioning. We further dissected nucleosome-protected sequences and identified a strong positive purine (AG) gradient from the 5′-end to the 3′-end, and also learnt that the nucleosome-enriched regions are GC-rich as compared to the nucleosome-free sequences as purine content is positively correlated with GC content. Sequence characterization allowed us to develop a hidden Markov model (HMM) algorithm for decoding nucleosome positioning computationally, and based on a set of training data from the fifth chromosome of C. elegans, our algorithm predicted 60%-70% of the well-positioned nucleosomes, which is 15%-20% higher than random positioning. We concluded that nucleosomes are not randomly positioned on DNA sequences and yet bind to different genome regions with variable stability, well-positioned nucleosomes leave sequence signatures on DNA, and statistical positioning of nucleosomes across genome can be decoded computationally based on these sequence signatures. 相似文献
19.
Mashkova TD Oparina NY Lacroix MH Fedorova LI G Tumeneva I Zinovieva OL Kisselev LL 《Journal of molecular biology》2001,305(1):33-48
Centromeric region of human chromosome 21 comprises two long alphoid DNA arrays: the well homogenized and CENP-B box-rich alpha21-I and the alpha21-II, containing a set of less homogenized and CENP-B box-poor subfamilies located closer to the short arm of the chromosome. Continuous alphoid fragment of 100 monomers bordering the non-satellite sequences in human chromosome 21 was mapped to the pericentromeric short arm region by fluorescence in situ hybridization (alpha21-II locus). The alphoid sequence contained several rearrangements including five large deletions within monomers and insertions of three truncated L1 elements. No binding sites for centromeric protein CENP-B were found. We analyzed sequences with alphoid/non-alphoid junctions selectively screened from current databases and revealed various rearrangements disrupting the regular tandem alphoid structure, namely, deletions, duplications, inversions, expansions of short oligonucleotide motifs and insertions of different dispersed elements. The detailed analysis of more than 1100 alphoid monomers from junction regions showed that the vast majority of structural alterations and joinings with non-alphoid DNAs occur in alpha satellite families lacking CENP-B boxes. Most analyzed events were found in sequences located toward the edges of the centromeric alphoid arrays. Different dispersed elements were inserted into alphoid DNA at kinkable dinucleotides (TG, CA or TA) situated between pyrimidine/purine tracks. DNA rearrangements resulting from different processes such as recombination and replication occur at kinkable DNA sites alike insertions but irrespectively of the occurrence of pyrimidine/purine tracks. It seems that kinkable dinucleotides TG, CA and TA are part of recognition signals for many proteins involved in recombination, replication, and insertional events. Alphoid DNA is a good model for studying these processes. 相似文献