Abstract
Z-DNAs are nucleic acid secondary structures that form within a special pattern of nucleotides and are promoted by DNA supercoiling. Through Z-DNA formation, DNA encodes information by dynamic changes in its secondary structure. A growing body of evidence indicates that Z-DNA formation can play a role in gene regulation; it can affect chromatin architecture and demonstrates its association with genomic instability, genetic diseases, and genome evolution. Many functional roles of Z-DNA are yet to be discovered highlighting the need for techniques to detect genome-wide folding of DNA into this structure. Here, we describe an approach to convert linear genome into supercoiled genome sponsoring Z-DNA formation. Applying permanganate-based methodology and high-throughput sequencing to supercoiled genome allows genome-wide detection of single-stranded DNA. Single-stranded DNA is characteristic of the junctions between the classical B-form of DNA and Z-DNA. Consequently, analysis of single-stranded DNA map provides snapshots of the Z-DNA conformation over the whole genome.
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References
Baranello L, Levens D, Gupta A, Kouzine F (2012) The importance of being supercoiled: how DNA mechanics regulate dynamic processes. Biochim Biophys Acta 1819(7):632–638. https://doi.org/10.1016/j.bbagrm.2011.12.007
Kouzine F, Levens D (2007) Supercoil-driven DNA structures regulate genetic transactions. Front Biosci 12:4409–4423. https://doi.org/10.2741/2398
Teves SS, Henikoff S (2014) Transcription-generated torsional stress destabilizes nucleosomes. Nat Struct Mol Biol 21(1):88–94. https://doi.org/10.1038/nsmb.2723
Kouzine F, Gupta A, Baranello L, Wojtowicz D, Ben-Aissa K, Liu J, Przytycka TM, Levens D (2013) Transcription-dependent dynamic supercoiling is a short-range genomic force. Nat Struct Mol Biol 20(3):396–403. https://doi.org/10.1038/nsmb.2517
Naughton C, Avlonitis N, Corless S, Prendergast JG, Mati IK, Eijk PP, Cockroft SL, Bradley M, Ylstra B, Gilbert N (2013) Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures. Nat Struct Mol Biol 20(3):387–395. https://doi.org/10.1038/nsmb.2509
Rich A, Zhang S (2003) Timeline: Z-DNA: the long road to biological function. Nat Rev Genet 4(7):566–572. https://doi.org/10.1038/nrg1115
Ho PS, Ellison MJ, Quigley GJ, Rich A (1986) A computer aided thermodynamic approach for predicting the formation of Z-DNA in naturally occurring sequences. EMBO J 5(10):2737–2744
Beknazarov N, ** S, Poptsova M (2020) Deep learning approach for predicting functional Z-DNA regions using omics data. Sci Rep UK 10(1):19134. https://doi.org/10.1038/s41598-020-76203-1
Zhabinskaya D, Benham CJ (2011) Theoretical analysis of the stress induced B-Z transition in superhelical DNA. PLoS Comput Biol 7(1):e1001051. https://doi.org/10.1371/journal.pcbi.1001051
Zhabinskaya D, Benham CJ (2013) Competitive superhelical transitions involving cruciform extrusion. Nucleic Acids Res 41(21):9610–9621. https://doi.org/10.1093/nar/gkt733
Liu H, Mulholland N, Fu H, Zhao K (2006) Cooperative activity of BRG1 and Z-DNA formation in chromatin remodeling. Mol Cell Biol 26(7):2550–2559. https://doi.org/10.1128/MCB.26.7.2550-2559.2006
Mulholland N, Xu Y, Sugiyama H, Zhao K (2012) SWI/SNF-mediated chromatin remodeling induces Z-DNA formation on a nucleosome. Cell Biosci 2:3. https://doi.org/10.1186/2045-3701-2-3
Kouzine F, Wojtowicz D, Baranello L, Yamane A, Nelson S, Resch W, Kieffer-Kwon KR, Benham CJ, Casellas R, Przytycka TM, Levens D (2017) Permanganate/S1 nuclease footprinting reveals non-B DNA structures with regulatory potential across a mammalian genome. Cell Syst 4(3):344–356. e347. https://doi.org/10.1016/j.cels.2017.01.013
Edwards SF, Sirito M, Krahe R, Sinden RR (2009) A Z-DNA sequence reduces slipped-strand structure formation in the myotonic dystrophy type 2 (CCTG) x (CAGG) repeat. Proc Natl Acad Sci U S A 106(9):3270–3275. https://doi.org/10.1073/pnas.0807699106
Zhao J, Bacolla A, Wang G, Vasquez KM (2010) Non-B DNA structure-induced genetic instability and evolution. Cell Mol Life Sci 67(1):43–62. https://doi.org/10.1007/s00018-009-0131-2
**e KT, Wang G, Thompson AC, Wucherpfennig JI, Reimchen TE, MacColl ADC, Schluter D, Bell MA, Vasquez KM, Kingsley DM (2019) DNA fragility in the parallel evolution of pelvic reduction in stickleback fish. Science 363(6422):81–84. https://doi.org/10.1126/science.aan1425
Wittig B, Wolfl S, Dorbic T, Vahrson W, Rich A (1992) Transcription of human c-myc in permeabilized nuclei is associated with formation of Z-DNA in three discrete regions of the gene. EMBO J 11(12):4653–4663
Wolfl S, Wittig B, Rich A (1995) Identification of transcriptionally induced Z-DNA segments in the human c-myc gene. Biochim Biophys Acta 1264(3):294–302. https://doi.org/10.1016/0167-4781(95)00155-7
van Holde K, Zlatanova J (1994) Unusual DNA structures, chromatin and transcription. BioEssays 16(1):59–68. https://doi.org/10.1002/bies.950160110
Shin SI, Ham S, Park J, Seo SH, Lim CH, Jeon H, Huh J, Roh TY (2016) Z-DNA-forming sites identified by ChIP-Seq are associated with actively transcribed regions in the human genome. DNA Res 23(5):477–486. https://doi.org/10.1093/dnares/dsw031
Li H, **ao J, Li J, Lu L, Feng S, Droge P (2009) Human genomic Z-DNA segments probed by the Z alpha domain of ADAR1. Nucleic Acids Res 37(8):2737–2746. https://doi.org/10.1093/nar/gkp124
Wu T, Lyu R, You Q, He C (2020) Kethoxal-assisted single-stranded DNA sequencing captures global transcription dynamics and enhancer activity in situ. Nat Methods 17(5):515–523. https://doi.org/10.1038/s41592-020-0797-9
Ha SC, Lowenhaupt K, Rich A, Kim YG, Kim KK (2005) Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases. Nature 437(7062):1183–1186. https://doi.org/10.1038/nature04088
Langmead B, Salzberg SL (2012) Fast gapped-read alignment with bowtie 2. Nat Methods 9(4):357–359. https://doi.org/10.1038/nmeth.1923
Li H, Durbin R (2009) Fast and accurate short read alignment with burrows-wheeler transform. Bioinformatics 25(14):1754–1760. https://doi.org/10.1093/bioinformatics/btp324
Ramirez F, Ryan DP, Gruning B, Bhardwaj V, Kilpert F, Richter AS, Heyne S, Dundar F, Manke T (2016) deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res 44(W1):W160–W165. https://doi.org/10.1093/nar/gkw257
Cer RZ, Bruce KH, Mudunuri US, Yi M, Volfovsky N, Luke BT, Bacolla A, Collins JR, Stephens RM (2011) Non-B DB: a database of predicted non-B DNA-forming motifs in mammalian genomes. Nucleic Acids Res 39(Database issue):D383–D391. https://doi.org/10.1093/nar/gkq1170
Anders S, Pyl PT, Huber W (2015) HTSeq – a python framework to work with high-throughput sequencing data. Bioinformatics 31(2):166–169. https://doi.org/10.1093/bioinformatics/btu638
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Kouzine, F., Wojtowicz, D., Przytycka, T.M., Levens, D. (2023). Detection of Z-DNA Structures in Supercoiled Genome. In: Kim, K.K., Subramani, V.K. (eds) Z-DNA. Methods in Molecular Biology, vol 2651. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3084-6_13
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DOI: https://doi.org/10.1007/978-1-0716-3084-6_13
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