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12 April 2024

A Model and Genomic Evidence for Sequence-Specific Chromatin Folding †

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1
DNA Resonance Research Foundation, San Diego, CA 92101, USA
2
OAK, Inc., Grants Pass, OR 97526, USA
3
Institute of Biochemical Technology and Nanotechnology, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Str., 117198 Moscow, Russia
4
Complementary and Integrative Health Clinic of Dr. Shishonin, 5 Yasnogorskaya Str., 117588 Moscow, Russia
The current study introduces a model in which the DNA sequence influences the structure of surrounding water in the nucleoplasm, proposing a mechanism where DNA’s molecular structure imprints some of itself on surrounding water clusters during a continuous dynamic chromatin reorganization process within the cell nucleus. It is known that water is an integral part of DNA structure(s). In vivo, the DNA double helix is covered with a layer of hydration, impermeable to a variety of cations, which is located around these double helices. It consists of about 18–19 water molecules per nucleotide in B-DNA and different amounts for other DNA structures. These water molecules are specifically arranged into phosphate groups and bases. Our hypothesis suggests that the spatial arrangement of DNA shapes the organization of water. Therefore, the focus is, namely, on the role of water in the structural stability and special organization of nucleic DNA. Its role in multiple molecular recognition processes, which involve nucleic DNA, is addressed. We developed molecular models of the sheath of water surrounding the double helix; based on this, they developed predictions about the sequence-specificity of chromatin folding and tested these predictions using public functional genomics data and computational genomic approaches. The results provided support for the proposed models of sequence-specific chromatin folding. These findings suggest a structural mechanism of interaction between DNA and its aqueous environment, offering an additional sequence-specific structural basis for chromatin dynamics and function.

Author Contributions

Conceptualization, A.V.V., M.M.-R. and M.M.R.; methodology, A.V.V.; software, I.S.; validation, O.P., R.A.M. and M.M.-R.; formal analysis, I.S.; investigation, A.V.V.; resources, M.M.-R.; data curation, M.M.-R.; writing—original draft preparation, A.A.V. and M.M.-R.; writing—review and editing, A.A.V. and M.M.-R.; visualization, I.S.; supervision, M.M.-R.; project administration, M.M.-R.; funding acquisition, M.M.-R. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

The data presented in this study are available in the article.

Acknowledgments

The publication has been prepared with the support of the «RUDN University Strategic Academic Leadership Program» (for A.A.V.).

Conflicts of Interest

The authors and OAK, Inc. declare no conflict of interest.
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