Hydroxylation of methylated CpG dinucleotides reverses stabilisation of DNA duplexes by cytosine 5-methylation.

Cytosine-5-methylation stabilises DNA duplexes and is associated with transcriptional repression; 5-methylcytosine undergoes hydroxylation to 5-hydroxymethylcytosine, a modification of unknown biological function. Spectroscopic and calorimetric analyses show that 5-hydroxymethylcytosine introduction reverses the stabilising effect of 5-methylcytosine, suggesting that in some contexts, 5-methylcytosine hydroxylation may, along with other factors, contribute to the alleviation of transcriptional repression.

[1]  C. Schofield,et al.  Structural studies on human 2-oxoglutarate dependent oxygenases. , 2010, Current opinion in structural biology.

[2]  Carles Acosta-Silva,et al.  Mutual relationship between stacking and hydrogen bonding in DNA. Theoretical study of guanine-cytosine, guanine-5-methylcytosine, and their dimers. , 2010, The journal of physical chemistry. B.

[3]  Haikuo Zhang,et al.  TET1 is a DNA-binding protein that modulates DNA methylation and gene transcription via hydroxylation of 5-methylcytosine , 2010, Cell Research.

[4]  T. Haferlach,et al.  Molecular genetics in acute myeloid leukemia , 2010, Current opinion in oncology.

[5]  I. Campbell,et al.  Asparaginyl beta-hydroxylation of proteins containing ankyrin repeat domains influences their stability and function. , 2009, Journal of molecular biology.

[6]  M. Esteller Epigenetic gene silencing in cancer: the DNA hypermethylome. , 2007, Human molecular genetics.

[7]  N. Heintz,et al.  The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain , 2009, Science.

[8]  H. Klump,et al.  Reversible helix/coil transitions of left-handed Z-DNA structures. Comparison of the thermodynamic properties of poly(dG).poly(dC), poly[d(G-C)].poly[d(G-C)], and poly(dG-m5dC).poly(dG-m5dC). , 1985, Biological chemistry Hoppe-Seyler.

[9]  N. Tretyakova,et al.  Endogenous cytosine methylation and the formation of carcinogen carcinogen-DNA adducts. , 2008, Nucleic acids symposium series.

[10]  David R. Liu,et al.  Conversion of 5-Methylcytosine to 5- Hydroxymethylcytosine in Mammalian DNA by the MLL Partner TET1 , 2009 .

[11]  R. Yung,et al.  DNA methylation and the regulation of gene transcription , 2002, Cellular and Molecular Life Sciences CMLS.

[12]  References , 1971 .

[13]  A. Kohlmann,et al.  Mutations of the TET2 and CBL genes: novel molecular markers in myeloid malignancies , 2010, Annals of Hematology.

[14]  H Shindo,et al.  Nucleic Acids , 1932, Nature.

[15]  G. A. van der Marel,et al.  Effect of 5-methylcytosine on the stability of triple-stranded DNA--a thermodynamic study. , 1991, Nucleic acids research.

[16]  T. Creighton Methods in Enzymology , 1968, The Yale Journal of Biology and Medicine.

[17]  Yi Zhang,et al.  Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification , 2010, Nature.

[18]  T. Brown,et al.  Improved synthesis of 5-hydroxymethyl-2'-deoxycytidine phosphoramidite using a 2'-deoxyuridine to 2'-deoxycytidine conversion without temporary protecting groups. , 2011, Bioorganic & medicinal chemistry letters.

[19]  D J Prockop,et al.  Collagens: molecular biology, diseases, and potentials for therapy. , 1995, Annual review of biochemistry.

[20]  A. Lloyd,et al.  Direct detection and quantification of methylation in nucleic acid sequences using high-resolution melting analysis. , 2010, Analytical chemistry.

[21]  Dongmei Cui,et al.  Supplementary Material (ESI) for Chemical Communications , 2009 .

[22]  G. Fasman,et al.  Handbook of biochemistry and molecular biology. Nucleic acids - v. 1 - 3. ed. , 1975 .

[23]  M. Esteller,et al.  Epigenetic modifications and human disease , 2010, Nature Biotechnology.

[24]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[25]  A. Bird,et al.  Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). , 2004, Nucleic acids research.