AFRJMS African Research Journal of Medical Sciences 3006-7421 Bioscience Press afrjms-1-2-003 10.62587/AFRJMS.1.2.2024.20-34 Review Article Exploring the dynamic 3D DNA structures in genomics: towards new diagnostic and therapeutic frontiers OdahMohammad Ahmad Ahmad 1 * 1Preparatory Year Deanship, Basic Science Department, Prince Sattam Bin Abdulaziz University, 151 Alkharj 11942, KSA. E-mail: m.odah@psau.edu.sa *Corresponding author: Mohammad Ahmad Ahmad Odah, Preparatory Year Deanship, Basic Science Department, Prince Sattam Bin Abdulaziz University, 151 Alkharj 11942, KSA. E-mail: m.odah@psau.edu.sa 07 2024 1 2 20 34 Abstract

The exploration of three-dimensional (3D) DNA structures marks a pivotal shift in genomics, offering unprecedented insights into the intricacies of cellular regulation, disease genesis, and the potential for novel diagnostic and therapeutic strategies. This study delves into the dynamic nature of 3D genome organization, investigating how these structures influence cellular functions in response to environmental changes and over time. Through a combination of real-time imaging and advanced computational models, we aim to unravel the complex interplay between 3D DNA structures, non-coding RNAs, and chromatin organization, and their collective impact on gene expression and cellular differentiation. A significant focus is placed on understanding the role of 3D DNA structures in the development and progression of genetic disorders. By employing comprehensive genomic and epigenomic profiling, this research seeks to identify structural aberrations linked to diseases, paving the way for the development of targeted diagnostics and therapies. Additionally, the study explores the potential of genome editing technologies, such as CRISPR-Cas systems, in correcting these structural abnormalities, while also addressing the ethical, legal, and social implications (ELSI) of such interventions. Integrating data from various genomic analyses, we propose the development of advanced computational models to predict the effects of 3D DNA structures on gene expression and cellular function. This integrative approach not only promises to enhance our understanding of genomic regulation but also sets the stage for groundbreaking advances in genomics-based diagnostics and therapeutics. The findings of this study have the potential to revolutionize our approach to treating genetic disorders, offering a new frontier in personalized medicine.

 Key words 3D DNA structures Genome editing (CRISPR-Cas) Genomic regulation Genetic disorders Computational genomics Non-coding RNA interactions Ethical Legal Social implications (ELSI) References Arzate-MejíaR.G.Recillas-TargaF.CorcesV. (2018). Developing in 3D: the role of CTCF in cell differentiation. Development, 145. doi: 10.1242/dev.137729. BarthJ.M.KohlerK. (2014). How to take autophagy and endocytosis up a Notch. BioMed. research international, 2014: 960803. https://doi.org/10.1155/2014/960803 Colino-SanguinoY.ClarkS.J.Valdes-MoraF. (2022). The H2A.Z-nucleosome code in mammals: emerging functions. Trends genet., Mar, 38(3): 273–289. doi: 10.1016/j.tig.2021.10.003. Cubeñas-PottsC.MatunisM. (2013). SUMO: a multifaceted modifier of chromatin structure and function. Developmental cell, Jan, 24(1): 1–12. doi: 10.1016/j.devcel.2012.11.020. FryR.BegleyT.SamsonL. (2005). Genome-wide responses to DNA-damaging agents. Annual review of microbiology, 59: 357–77. doi: 10.1146/ANNUREV.MICRO.59.031805.133658. FuY.TessneerK.L.LiC.GaffneyP. (2018). From association to mechanism in complex disease genetics: the role of the 3D genome. Arthritis research & therapy, 20. doi: 10.1186/s13075-018-1721-x. HansenA.S.CattoglioC.DarzacqX.TjianR. (2017). Recent evidence that TADs and chromatin loops are dynamic structures. Nucleus, 9: 20–32. doi: 10.1080/19491034.2017.1389365. HegedûsK.TakátsS.BodaA.JipaA.NagyP.VargaK.KovácsA.L.JuhászG. (2014). The putative HORMA domain protein Atg101 dimerizes and is required for starvation-induced and selective autophagy in Drosophila. Autophagy, 10(8): 1330–1342. https://doi.org/10.4161/auto.29141 KamagataK.MurataA.ItohY.TakahashiS. (2017). Characterization of facilitated diffusion of tumor suppressor p53 along DNA using single-molecule fluorescence imaging. Journal of photochemistry and photobiology C-photochemistry reviews, 30: 36–50. doi: 10.1016/JJPHOTOCHEMREV.2017.01.004. KimJ.B.SteinR.O’hareM.J. (2004). Three-dimensional in vitro tissue culture models of breast cancer — a review. Breast cancer research and treatment, 85: 281–291. doi: 10.1023/B:BREA.0000025418.88785.2b. KovacsA.L. (2014). A simple method to estimate the number of autophagic elements by electron microscopic morphometry in real cellular dimensions. BioMed research international, 2014: 182760. https://doi.org/10.1155/2014/182760 LippaiM.LõwP. (2014). The role of the selective adaptor p62 and ubiquitin-like proteins in autophagy. BioMed Research International, 2014: 832704. https://doi.org/10.1155/2014/832704 LõrinczP.LakatosZ.MaruzsT.SzatmáriZ.KisV.SassM. (2014). Atg6/UVRAG/Vps34-containing lipid kinase complex is required for receptor downregulation through endolysosomal degradation and epithelial polarity during Drosophila wing development. BioMed research international, 2014: 851349. https://doi.org/10.1155/2014/851349 MigliettaG.RussoM.CapranicoG. (2020). G-quadruplex–R-loop interactions and the mechanism of anticancer G-quadruplex binders. Nucleic acids research, 48: 11942–11957. doi: 10.1093/nar/gkaa944. MigliettaG.RussoM.CapranicoG. (2020). G-quadruplex–R-loop interactions and the mechanism of anticancer G-quadruplex binders. Nucleic acids research, 48: 11942–11957. https://doi.org/10.1093/nar/gkaa944 MigliettaG.RussoM.CapranicoG. (2020). G-quadruplex–R-loop interactions and the mechanism of anticancer G-quadruplex binders. Nucleic acids research, 49: 595–595. https://doi.org/10.1093/nar/gkaa1206 MorselliM.DieciG. (2022). Epigenetic regulation of human non-coding RNA gene transcription. Biochemical society transactions. doi: 10.1042/BST20210860. MulakkalN.C.NagyP.TakatsS.TuscoR.JuhászG.NezisI.P. (2014). Autophagy in Drosophila: from historical studies to current knowledge. BioMed research international, 2014: 273473. https://doi.org/10.1155/2014/273473 NezisI.P.VaccaroM.I.DevenishR.J.JuhászG. (2014). Autophagy in development, cell differentiation, and homeodynamics: from molecular mechanisms to diseases and pathophysiology. BioMed research international, 2014. doi: 10.1155/2014/349623. OjoloS.P.CaoS.PriyadarshaniS.LiW.YanM.AslamM.ZhaoH.QinY. (2018). Regulation of plant growth and development: a review from a chromatin remodeling perspective. Frontiers in plant science, 9. doi: 10.3389/fpls.2018.01232. PikeJ.LeeS.MeyerM. (2014). Regulation of gene expression by 1,25-dihydroxyvitamin D3 in bone cells: exploiting new approaches and defining new mechanisms. BoneKEy reports, 3: 482. doi: 10.1038/bonekey.2013.216. PikeJ.ZellaL.A.MeyerM.FretzJ.A.KimS. (2007). Molecular actions of 1,25 dihydroxyvitamin D3 on genes involved in calcium homeostasis. Journal of bone and mineral research, 22. doi: 10.1359/jbmr.07s207. QinY.HurleyL.H. (2008). Structures, folding patterns, and functions of intramolecular DNA G-quadruplexes found in eukaryotic promoter regions. Biochimie., Aug;, 90(8): 1149–71. doi: 10.1016/j.biochi.2008.02.020. RavichandranS.AhnJ.-H.KimK. (2019). Unraveling the regulatory G-quadruplex puzzle: lessons from genome and transcriptome-wide studies. Frontiers in genetics, 10. doi: 10.3389/fgene.2019.01002. RomanelliD.CasatiB.FranzettiE.TettamantiG. (2014). A molecular view of autophagy in Lepidoptera. BioMed research international, 2014: 902315. https://doi.org/10.1155/2014/902315 RossmannM.ZonL. (2021). ‘Enhancing’ red cell fate through epigenetic mechanisms. Current opinion in hematology, 28: 129–137. doi: 10.1097/MOH.0000000000000654. SagonaA.P.NezisI.P. (2014). Association of CHMP4B and autophagy with micronuclei: implications for cataract formation. BioMed research international, 2014: 974393. https://doi.org/10.1155/2014/974393 SobolewskaA.GajewskaM.ZarzyñskaJ.GajkowskaB. (2009). Motyl T. IGF-I, EGF, and sex steroids regulate autophagy in bovine mammary epithelial cells via the mTOR pathway. Eur. j. cell biol., Feb, 88(2): 117–30. doi: 10.1016/j.ejcb.2008.09.004. WangC.-Y.TangZ.ZhaoY.YaoR.LiL.SunW. (2014). Three-dimensional in vitro cancer models: a short review. Biofabrication, 6. doi: 10.1088/1758-5082/6/2/022001. YanS.YuanD. (2021). Continuous microfluidic 3D focusing enabling microflow cytometry for singlecell analysis. Talanta, 221: 121401. doi: 10.1016/j.talanta.2020.121401. ZielniokK.MotylT.GajewskaM. (2014). Functional interactions between 17β-estradiol and progesterone regulate autophagy during acini formation by bovine mammary epithelial cells in 3D cultures. Autophagy., 10(5): 846–860. https://doi.org/10.4161/auto.28269