Non-canonical aberrant DNA hypermethylation in glioma

Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC in primary samples from 54 gliomas and 72 colorectal cancer patients. Levels of 5hmC in colorectal cancer were very low and no consistent changes were detected between control tissues and tumors. As expected, levels of 5hmC in non-tumoral brain samples were high and significantly reduced at the 49,601 CpG sites in gliomas. Strikingly, hypo-hydroxymethylation at 4,627 (9.3%) of these CpG sites was associated with aberrant DNA hypermethylation. The DNA regions containing these CpG sites were enriched in H3K4me2, and presented a different genuine chromatin signature to that characteristic of the genes classically aberrantly hypermethylated in cancer. We conclude that this data identifies a novel 5hmC-dependent non-canonical class of aberrant DNA hypermethylation in glioma.

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

[2]  G. R. Wyatt,et al.  A New Pyrimidine Base from Bacteriophage Nucleic Acids , 1952, Nature.

[3]  J. Herman,et al.  Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. , 1996, Cancer research.

[4]  Thomas de Quincey.  [C] , 2000, The Works of Thomas De Quincey, Vol. 1: Writings, 1799–1820.

[5]  장윤희,et al.  Y. , 2003, Industrial and Labor Relations Terms.

[6]  A. ADoefaa,et al.  ? ? ? ? f ? ? ? ? ? , 2003 .

[7]  A. Feinberg,et al.  The history of cancer epigenetics , 2004, Nature Reviews Cancer.

[8]  M. Esteller.  Aberrant DNA methylation as a cancer-inducing mechanism. , 2005, Annual review of pharmacology and toxicology.

[9]  Christian B. Woods,et al.  Analysis of repetitive element DNA methylation by MethyLight , 2005, Nucleic acids research.

[10]  Kelly M. McGarvey,et al.  Silenced tumor suppressor genes reactivated by DNA demethylation do not return to a fully euchromatic chromatin state. , 2006, Cancer research.

[11]  P. Laird,et al.  Epigenetic stem cell signature in cancer , 2007, Nature Genetics.

[12]  John D. Storey,et al.  Capturing Heterogeneity in Gene Expression Studies by Surrogate Variable Analysis , 2007, PLoS genetics.

[13]  Kelly M. McGarvey,et al.  A stem cell–like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing , 2007, Nature Genetics.

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

[15]  M. Ehrlich.  DNA hypomethylation in cancer cells. , 2009, Epigenomics.

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

[17]  M. Biel,et al.  Tissue Distribution of 5-Hydroxymethylcytosine and Search for Active Demethylation Intermediates , 2010, PloS one.

[18]  C. Glass,et al.  Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. , 2010, Molecular cell.

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

[20]  Harris A. Jaffee,et al.  Redefining CpG islands using hidden Markov models. , 2010, Biostatistics.

[21]  Xiao Zhang,et al.  Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis , 2010, BMC Bioinformatics.

[22]  C. Sotiriou,et al.  Evaluation of the Infinium Methylation 450K technology. , 2011, Epigenomics.

[23]  C. Iacobuzio-Donahue,et al.  Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers , 2011, Oncotarget.

[24]  P. Jin,et al.  Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine , 2011, Nature Biotechnology.

[25]  Manolis Kellis,et al.  Discovery and Characterization of Chromatin States for Systematic Annotation of the Human Genome , 2011, RECOMB.

[26]  Weiwei Li,et al.  Distribution of 5-Hydroxymethylcytosine in Different Human Tissues , 2011, Journal of nucleic acids.

[27]  Timothy J. Durham,et al.  Systematic analysis of chromatin state dynamics in nine human cell types , 2011, Nature.

[28]  K. Gunderson,et al.  High density DNA methylation array with single CpG site resolution. , 2011, Genomics.

[29]  G. Schackert,et al.  5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations. , 2011, Cancer research.

[30]  W. Reik,et al.  Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation , 2011, Nature.

[31]  B. Blencowe,et al.  5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary , 2012, Nature Structural &Molecular Biology.

[32]  Abraham J. Khorasani,et al.  Loss of 5-Hydroxymethylcytosine Is an Epigenetic Hallmark of Melanoma , 2012, Cell.

[33]  H. Aburatani,et al.  Loss of 5‐hydroxymethylcytosine is accompanied with malignant cellular transformation , 2012, Cancer science.

[34]  M. Rehli,et al.  5-Hydroxymethylcytosine is an essential intermediate of active DNA demethylation processes in primary human monocytes , 2013, Genome Biology.

[35]  Sven Rahmann,et al.  Snakemake--a scalable bioinformatics workflow engine. , 2012, Bioinformatics.

[36]  Colm E. Nestor,et al.  Tissue type is a major modifier of the 5-hydroxymethylcytosine content of human genes. , 2012, Genome research.

[37]  A. Oshlack,et al.  SWAN: Subset-quantile Within Array Normalization for Illumina Infinium HumanMethylation450 BeadChips , 2012, Genome Biology.

[38]  U. Schüller,et al.  Low values of 5‐hydroxymethylcytosine (5hmC), the “sixth base,” are associated with anaplasia in human brain tumors , 2012, International journal of cancer.

[39]  Martin J. Aryee,et al.  A DNA hypermethylation module for the stem/progenitor cell signature of cancer , 2011, Genome research.

[40]  W. Nelson,et al.  Decreased 5-Hydroxymethylcytosine Is Associated with Neural Progenitor Phenotype in Normal Brain and Shorter Survival in Malignant Glioma , 2012, PloS one.

[41]  Z. Ling,et al.  Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation , 2013, Oncogene.

[42]  Limei Liu,et al.  Decrease of 5-Hydroxymethylcytosine Is Associated with Progression of Hepatocellular Carcinoma through Downregulation of TET1 , 2013, PloS one.

[43]  Chuan He,et al.  HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis , 2013, Proceedings of the National Academy of Sciences.

[44]  K. Hansen,et al.  Functional normalization of 450k methylation array data improves replication in large cancer studies , 2014, Genome Biology.

[45]  Nongluk Plongthongkum,et al.  Advances in the profiling of DNA modifications: cytosine methylation and beyond , 2014, Nature Reviews Genetics.

[46]  J. Koenderink.  Q… , 2014, Les noms officiels des communes de Wallonie, de Bruxelles-Capitale et de la communaute germanophone.

[47]  Lee E. Edsall,et al.  5mC oxidation by Tet2 modulates enhancer activity and timing of transcriptome reprogramming during differentiation. , 2014, Molecular cell.

[48]  Rochelle L. Tiedemann,et al.  Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells , 2014, Genome Biology.

[49]  S. Balasubramanian,et al.  5-Hydroxymethylcytosine is a predominantly stable DNA modification. , 2014, Nature chemistry.

[50]  M. Fraga,et al.  Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility. , 2015, Human reproduction.

[51]  S. Balasubramanian,et al.  Accurate Measurement of 5-Methylcytosine and 5-Hydroxymethylcytosine in Human Cerebellum DNA by Oxidative Bisulfite on an Array (OxBS-Array) , 2015, PloS one.

[52]  이화영.  X , 1960, Chinese Plants Names Index 2000-2009.

[53]  Matthew E. Ritchie,et al.  limma powers differential expression analyses for RNA-sequencing and microarray studies , 2015, Nucleic acids research.

[54]  H. Kretzschmar,et al.  Loss of 5-hydroxymethylcytosine and intratumoral heterogeneity as an epigenomic hallmark of glioblastoma , 2015, Tumor Biology.

[55]  K. Herrup,et al.  Alteration in 5-hydroxymethylcytosine-mediated epigenetic regulation leads to Purkinje cell vulnerability in ATM deficiency. , 2015, Brain : a journal of neurology.

[56]  Gustavo F. Bayón,et al.  H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells , 2015, Genome research.

[57]  S. Balasubramanian,et al.  oxBS-450K: A method for analysing hydroxymethylation using 450K BeadChips , 2015, Methods.

[58]  S. Vowler,et al.  5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer , 2015, Genome Biology.

[59]  M. Bissonnette,et al.  TET-catalyzed 5-hydroxymethylcytosine regulates gene expression in differentiating colonocytes and colon cancer , 2015, Scientific Reports.

[60]  M. Fraga,et al.  Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells , 2016, Journal of Translational Medicine.

[61]  Gordon R. McInroy,et al.  Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma , 2017, npj Genomic Medicine.

[62]  Sven Rahmann,et al.  Genome analysis , 2022 .

[63]  W. Hager,et al.  and s , 2019, Shallow Water Hydraulics.