In silico structural analysis of sequences containing 5-hydroxymethylcytosine reveals its potential as binding regulator for development, ageing and cancer-related transcription factors

References

• Luo C, Hajkova P, Ecker JR. Dynamic DNA methylation: in the right place at the right time. Science. 2018;361:1336–1340.
   Google Scholar
• Anastasiadou C, Malousi A, Maglaveras N, et al. Human epigenome data reveal increased CpG methylation in alternatively spliced sites and putative exonic splicing enhancers. DNA Cell Biol. 2011;30:267–275.
   Google Scholar
• Lev Maor G, Yearim A, Ast G. The alternative role of DNA Methylation in splicing regulation. Trends Genet. 2015;31:274–280.
   Google Scholar
• Salami F, Qiao S, Homayouni R. Expression of mouse Dab2ip transcript variants and gene methylation during brain development. Gene. 2015;568:19–24.
   Google Scholar
• Parry L, Clarke AR. The roles of the methyl-CpG binding proteins in cancer. Genes Cancer. 2011;2:618–630.
   Google Scholar
• Malygin EG, Hattman S. DNA methyltransferases: mechanistic models derived from kinetic analysis. Crit Rev Biochem Mol Biol. 2012;47:97–193.
   Google Scholar
• Klungland A, Robertson AB. Oxidized C5-methyl cytosine bases in DNA: 5-hydroxymethylcytosine; 5-formylcytosine; and 5-carboxycytosine. Free Radic Biol Med. 2017;107:62–68.
   Google Scholar
• Ji D, You C, Wang P, et al. Effects of tet-induced oxidation products of 5-methylcytosine on DNA replication in mammalian cells. Chem Res Toxicol. 2014;27:1304–1309.
   Google Scholar
• Melamed P, Yosefzon Y, David C, et al. Tet enzymes, variants, and differential effects on function. Front Cell Dev Biol. 2018;6:22.
   Google Scholar
• Shukla A, Sehgal M, Singh TR. Hydroxymethylation and its potential implication in DNA repair system: a review and future perspectives. Gene. 2015;564:109–118.
   Google Scholar
• Li W, Zhang X, Lu X, et al. 5-hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers. Cell Res. 2017;27:1243–1257.
   Google Scholar
• Tammen SA, Dolnikowski GG, Ausman LM, et al. Aging alters hepatic DNA hydroxymethylation, as measured by liquid chromatography/mass spectrometry. J Cancer Prev. 2014;19:301–308.
   Google Scholar
• Ponnaluri VKC, Ehrlich KC, Zhang G, et al. Association of 5-hydroxymethylation and 5-methylation of DNA cytosine with tissue-specific gene expression. Epigenetics. 2017;12:123–138.
   Google Scholar
• Gackowski D, Zarakowska E, Starczak M, et al. Tissue-specific differences in DNA modifications (5-hydroxymethylcytosine, 5-formylcytosine, 5-carboxylcytosine and 5-hydroxymethyluracil) and their interrelationships. PloS One. 2015;10:e0144859.
   Google Scholar
• DeNizio JE, Liu MY, Leddin EM, et al. Selectivity and promiscuity in TET-mediated oxidation of 5-methylcytosine in DNA and RNA. Biochemistry. 2019;58:411–421.
   Google Scholar
• Ngo TTM, Yoo J, Dai Q, et al. Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability. Nat Commun. 2016;7:10813.
   Google Scholar
• Falabella M, Kolesar JE, Wallace C, et al. G-quadruplex dynamics contribute to regulation of mitochondrial gene expression. Sci Rep. 2019;9:5605.
   Google Scholar
• Kwok CK, Merrick CJ. G-quadruplexes: prediction, characterization, and biological application. Trends Biotechnol. 2017;35:997–1013.
   Google Scholar
• Mao S-Q, Ghanbarian AT, Spiegel J, et al. DNA G-quadruplex structures mold the DNA methylome. Nat Struct Mol Biol. 2018;25:951–957.
   Google Scholar
• Cheng M, Cheng Y, Hao J, et al., Loop permutation affects the topology and stability of G-quadruplexes. Nucleic Acids Res. 2018;46:9264–9275.
   Google Scholar
• Guo S, Lu H. Conjunction of potential G-quadruplex and adjacent cis-elements in the 5ʹ UTR of hepatocyte nuclear factor 4-alpha strongly inhibit protein expression. Sci Rep. 2017;7:17444.
   Google Scholar
• Hegyi H. Enhancer-promoter interaction facilitated by transiently forming G-quadruplexes. Sci Rep. 2015;5:9165.
   Google Scholar
• Halder K, Halder R, Chowdhury S. Genome-wide analysis predicts DNA structural motifs as nucleosome exclusion signals. Mol Biosyst. 2009;5:1703–1712.
   Google Scholar
• Collings CK, Anderson JN. Links between DNA methylation and nucleosome occupancy in the human genome. Epigenetics Chromatin. 2017;10:18.
   Google Scholar
• Tippana R, Xiao W, Myong S. G-quadruplex conformation and dynamics are determined by loop length and sequence. Nucleic Acids Res. 2014;42:8106–8114.
   Google Scholar
• Watanabe R, Kanno S-I, Mohammadi Roushandeh A, et al. Nucleosome remodelling, DNA repair and transcriptional regulation build negative feedback loops in cancer and cellular ageing. Philos Trans R Soc Lond B Biol Sci. 2017;372:20160473.
   Google Scholar
• Hänsel-Hertsch R, Beraldi D, Lensing SV, et al. G-quadruplex structures mark human regulatory chromatin. Nat Genet. 2016;48:1267–1272.
   Google Scholar
• Morgan RK, Molnar MM, Batra H, et al. Effects of 5-hydroxymethylcytosine epigenetic modification on the stability and molecular recognition of VEGF I-Motif and G-Quadruplex structures. J Nucleic Acids. 2018;2018:9281286.
   Google Scholar
• Varizhuk A, Isaakova E, Pozmogova G. DNA G-quadruplexes (G4s) modulate epigenetic (Re)programming and chromatin remodeling: transient genomic g4s assist in the establishment and maintenance of epigenetic marks, while persistent G4s may erase epigenetic marks. BioEssays. 2019;41:e1900091.
   Google Scholar
• Liu M-J, Seddon AE, Tsai ZT-Y, et al. Determinants of nucleosome positioning and their influence on plant gene expression. Genome Res. 2015;25:1182–1195.
   Google Scholar
• Li X, Liu Y, Salz T, et al. Whole-genome analysis of the methylome and hydroxymethylome in normal and malignant lung and liver. Genome Res. 2016;26:1730–1741.
   Google Scholar
• Quinlan AR. BEDTools: the swiss-army tool for genome feature analysis. Curr Protoc Bioinformatics. 2014;47:11.12.1–34.
   Google Scholar
• Hon J, Martínek T, Zendulka J, et al. Pqsfinder: an exhaustive and imperfection-tolerant search tool for potential quadruplex-forming sequences in R. Bioinformatics. 2017;33:3373–3379.
   Google Scholar
• Pages H, Aboyoun P, Gentleman R, et al., Biostrings: efficient manipulation of biological strings. 2019.
   Google Scholar
• Malousi A, Kouidou S, Tsagiopoulou M, et al. MeinteR: A framework to prioritize DNA methylation aberrations based on conformational and cis-regulatory element enrichment. Sci Rep. 2019;9:19148.
   Google Scholar
• Kaplan N, Moore IK, Fondufe-Mittendorf Y, et al. The DNA-encoded nucleosome organization of a eukaryotic genome. Nature. 2009;458:362–366.
   Google Scholar
• Dunham I, Kundaje A, Aldred SF, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.
   Google Scholar
• Smit AFA, Hubley R. RepeatModeler Open-1.0. 2008–2015; software Available from: http://www.repeatmasker.org.
   Google Scholar
• Benson G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 1999;27:573–580.
   Google Scholar
• Bailey TL, Boden M, Buske FA, et al. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 2009;37:W202–8.
   Google Scholar
• Grant CE, Bailey TL, Noble WS. FIMO: scanning for occurrences of a given motif. Bioinformatics. 2011;27:1017–1018.
   Google Scholar
• Chiu T-P, Xin B, Markarian N, et al., TFBSshape: an expanded motif database for DNA shape features of transcription factor binding sites preprint. 2019.
   Google Scholar
• R Core Team. a language and environment for statistical computing.: R foundation for statistical computing. 2018; software Available from: https://www.R-project.org.
   Google Scholar
• Struhl K, Segal E. Determinants of nucleosome positioning. Nat Struct Mol Biol. 2013;20:267–273.
   Google Scholar
• Ma Q, Xu Z, Lu H, et al. Distal regulatory elements identified by methylation and hydroxymethylation haplotype blocks from mouse brain. Epigenetics Chromatin. 2018;11:75.
   Google Scholar
• Kizaki S, Zou T, Li Y, et al. Preferential 5-methylcytosine oxidation in the linker region of reconstituted positioned nucleosomes by tet1 protein. Chemistry. 2016;22:16598–16601.
   Google Scholar
• Roque A, Orrego M, Ponte I, et al. The preferential binding of Histone H1 to DNA scaffold-associated regions is determined by its c-terminal domain. Nucleic Acids Res. 2004;32:6111–6119.
   Google Scholar
• Sedghi Masoud S, Nagasawa K. I-motif-binding ligands and their effects on the structure and biological functions of I-motif. Chem Pharm Bull (Tokyo). 2018;66:1091–1103.
   Google Scholar
• Klug A. The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation, Quart. Rev Biophys. 2010;43: 1–21.
   Google Scholar
• Martiénez-Balbás MA, Jiménez-Garciéa E, Azorin F. Zinc(II) ions selectively interact with DNA sequences present at the TFIIIA binding site of the Xenopus 5S-RNA gene. Nucl Acids Res. 1995;23:2464–2471.
   Google Scholar
• Brown ML, Schroth GP, Gottesfeld JM, et al. Protein and DNA requirements for the transcription factor IIIA-induced distortion of the 5 S rRNA gene promoter. J Mol Biol. 1996;262:600–614.
   Google Scholar
• Brukner I, Susic S, Dlakic M, et al. Physiological concentration of magnesium ions induces a strong macroscopic curvature in GGGCCC-containing DNA. J Mol Biol. 1994;236:26–32.
   Google Scholar
• Yu D, Sawitzke JA, Ellis H, et al. Recombineering with overlapping single-stranded DNA oligonucleotides: testing a recombination intermediate. Proc Natl Acad Sci U S A. 2003;100:7207–7212.
   Google Scholar
• Ludwig AK, Zhang P, Hastert FD, et al. Binding of MBD proteins to DNA Blocks Tet1 function thereby modulating transcriptional noise. Nucleic Acids Res. 2017;45:2438–2457.
   Google Scholar
• Owen-Hughes T, Gkikopoulos T. Making sense of transcribing chromatin. Curr Opin Cell Biol. 2012;24:296–304.
   Google Scholar
• Zheng Z, Ambigapathy G, Keifer J. MeCP2 regulates Tet1-catalyzed demethylation, CTCF binding, and learning-dependent alternative splicing of the BDNF gene in turtle. eLife. 2017;6. DOI:10.7554/eLife.25384
   Google Scholar
• Khrapunov S, Tao Y, Cheng H, et al. MeCP2 binding cooperativity inhibits DNA modification-specific recognition. Biochemistry. 2016;55:4275–4285.
   Google Scholar
• Lei M, Tempel W, Chen S, et al. Plasticity at the DNA recognition site of the MeCP2 MCG-binding domain, biochimica et biophysica acta. Gene Regul Mech. 2019;1862:194409.
   Google Scholar
• Riedmann C, Fondufe-Mittendorf YN. Comparative analysis of linker Histone H1, MeCP2, and HMGD1 on nucleosome stability and target site accessibility. Sci Rep. 2016;6:33186.
   Google Scholar
• Mellén M, Ayata P, Dewell S, et al. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell. 2012;151:1417–1430.
   Google Scholar
• Yang Y, Kucukkal TG, Li J, et al. Binding analysis of methyl-CpG binding domain of MeCP2 and rett syndrome mutations. ACS Chem Biol. 2016;11:2706–2715.
   Google Scholar
• Schmidt A, Zhang H, Cardoso MC. MeCP2 and Chromatin Compartmentalization. Cells. 2020;9:878.
   Google Scholar
• Khoueiry R, Sohni A, Thienpont B, et al. Lineage-specific functions of TET1 in the postimplantation mouse embryo. Nat Genet. 2017;49:1061–1072.
   Google Scholar
• Della Ragione F, Filosa S, Scalabrì F, et al. MeCP2 as a genome-wide modulator: the renewal of an old story. Front Genet. 2012;3:181.
   Google Scholar
• Campilongo R, Fung RKY, Little RH, et al. One ligand, two regulators and three binding sites: how KDPG controls primary carbon metabolism in pseudomonas. PLoS Genet. 2017;13:e1006839.
   Google Scholar
• Joseph SR, Pálfy M, Hilbert L, et al. Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos. eLife. 2017;6. DOI:10.7554/eLife.23326
   Google Scholar
• Perriaud L, Marcel V, Sagne C, et al. Impact of G-quadruplex structures and intronic polymorphisms Rs17878362 and Rs1642785 on basal and ionizing radiation-induced expression of alternative P53 transcripts. Carcinogenesis. 2014;35:2706–2715.
   Google Scholar
• Czech A, Konarev PV, Goebel I, et al. Octa-repeat domain of the mammalian prion protein mRNA forms stable a-helical hairpin structure rather than G-quadruplexes. Sci Rep. 2019;9:2465.
   Google Scholar
• Mukherjee AK, Sharma S, Chowdhury S. Non-Duplex G-Quadruplex structures emerge as mediators of epigenetic modifications. Trends Genet. 2019;35:129–144.
   Google Scholar
• Kouidou S, Malousi A, Maglaveras N. Methylation and repeats in silent and nonsense mutations of P53. Mutat Res. 2006;599:167–177.
   Google Scholar
• Stroud H, Feng S, Morey Kinney S, et al. 5-hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol. 2011;12:R54.
   Google Scholar
• Farnung L, Vos SM, Wigge C, et al. Nucleosome-Chd1 structure and implications for chromatin remodelling. Nature. 2017;550:539–542.
   Google Scholar
• McGinty RK, Tan S. Nucleosome structure and function. Chem Rev. 2015;115:2255–2273.
   Google Scholar
• Williams K, Christensen J, Pedersen MT, et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature. 2011;473:343–348.
   Google Scholar
• Wang X, Goodrich KJ, Gooding AR, et al. Targeting of polycomb repressive complex 2 to RNA by short repeats of consecutive guanines. Mol Cell. 2017;65:1056–1067.e5.
   Google Scholar
• Öberg C, Izzo A, Schneider R, et al. Linker histone subtypes differ in their effect on nucleosomal spacing in vivo. J Mol Biol. 2012;419:183–197.
   Google Scholar
• Eddy J, Vallur AC, Varma S, et al. G4 motifs correlate with promoter-proximal transcriptional pausing in human genes. Nucleic Acids Res. 2011;39:4975–4983.
   Google Scholar
• Lin I-H, Chen Y-F, Hsu M-T. Correlated 5-hydroxymethylcytosine (5hmC) and gene expression profiles underpin gene and organ-specific epigenetic regulation in adult mouse brain and liver. PloS One. 2017;12:e0170779.
   Google Scholar
• Yu B, Russanova VR, Gravina S, et al. DNA methylome and transcriptome sequencing in human ovarian granulosa cells links age-related changes in gene expression to gene body methylation and 3ʹ-End GC Density. Oncotarget. 2015;6:3627–3643.
   Google Scholar