Moderation of Structural DNA Properties by Coupled Dinucleotide Contents in Eukaryotes

Abstract

Dinucleotides are known as determinants for various structural and physiochemical properties of DNA and for binding affinities of proteins to DNA. These properties (e.g., stiffness) and bound proteins (e.g., transcription factors) are known to influence important biological functions, such as transcription regulation and 3D chromatin organization. Accordingly, the question arises of how the considerable variations in dinucleotide contents of eukaryotic chromosomes could still provide consistent DNA properties resulting in similar functions and 3D conformations. In this work, we investigate the hypothesis that coupled dinucleotide contents influence DNA properties in opposite directions to moderate each other’s influences. Analyzing all 2478 chromosomes of 155 eukaryotic species, considering bias from coding sequences and enhancers, we found sets of correlated and anti-correlated dinucleotide contents. Using computational models, we estimated changes of DNA properties resulting from this coupling. We found that especially pure A/T dinucleotides (AA, TT, AT, TA), known to influence histone positioning and AC/GT contents, are relevant moderators and that, e.g., the Roll property, which is known to influence histone affinity of DNA, is preferably moderated. We conclude that dinucleotide contents might indirectly influence transcription and chromatin 3D conformation, via regulation of histone occupancy and/or other mechanisms.

Condensed Matter Systems Exposed to Radiation: Multiscale Theory, Simulations, and Experiment

“…In this context, very short, short, intermediate, and long motifs are interspersed in the genome, which seem responsible for the appropriate spatial organization and folding of chromatin units. 659,660 This spatial organization can follow a specific dynamic regulation, opening and closing reactive chromatin units and thus controlling cell nuclear and cellular functioning. 661,662 Between the differently packed chromatin, there is enough "free" space for floating differently sized molecules, such as RNAs, proteins, enzymes, ATPs, water molecules, atoms, differently charged ions, or other entities, which are trafficking primarily by superdiffusion (i.e., anomalous diffusion supported and directed by active transport processes) or supradiffusion (anomalous diffusion hindered, e.g., by macromolecular crowding) to the correct interaction points where they are required.…”

“…The findings can be compared with known biophysical parameters of chromatin folding and arrangement. 660 Self-organization of chromatin in the cell nucleus 656 results in function-related networks 657 (e.g., heterochromatin or euchromatin network, 662 network of ALU-repeats, 657,678 network of L1-repeats, 678 etc.) and specific local topologies.…”

“…In addition to the sequence of the individual bases, information in the form of sequence motifs and motif arrangements plays a crucial role. In this context, very short, short, intermediate, and long motifs are interspersed in the genome, which seem responsible for the appropriate spatial organization and folding of chromatin units. , This spatial organization can follow a specific dynamic regulation, opening and closing reactive chromatin units and thus controlling cell nuclear and cellular functioning. , …”

“…Probes based on supershort-tandem-repeats may be applied to label these regions as indicators. The findings can be compared with known biophysical parameters of chromatin folding and arrangement …”

Specific Patterns in Correlations of Super-Short Tandem Repeats (SSTRs) with G+C Content, Genic and Intergenic Regions, and Retrotransposons on All Human Chromosomes

“…To test the statistical significance of correlation, we repeated the analysis described above (correlations of local densities with segment sizes of 100 kbp), using repeat contents, predicted by nucleotide-based (first-order Markov) models (as already described in [30]), instead of empirical contents. Using the variance of the modeled results, we derived a significance level, based on the null-hypothesis of tandem repeat contents based on nucleotide frequencies only, by dividing the difference between empirical correlations and model predictions by the respective error approximation (described in [30]).…”