Finding the fifth base: genome-wide sequencing of cytosine methylation.

Complete sequences of myriad eukaryotic genomes, including several human genomes, are now available, and recent dramatic developments in DNA sequencing technology are opening the floodgates to vast volumes of sequence data. Yet, despite knowing for several decades that a significant proportion of cytosines in the genomes of plants and animals are present in the form of methylcytosine, until very recently the precise locations of these modified bases have never been accurately mapped throughout a eukaryotic genome. Advanced "next-generation" DNA sequencing technologies are now enabling the global mapping of this epigenetic modification at single-base resolution, providing new insights into the regulation and dynamics of DNA methylation in genomes.

• Publication year

  2009

• Venue

  Genome Research

• Publication date

  2009-06-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1101/gr.083451.108PMID 19273618PMCID PMC3807530
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver.

  2009cited by this paper
• Corrigendum: Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells

  2009cited by this paper
• Targeted and genome-scale methylomics reveals gene body signatures in human cell lines

  2009cited by this paper
• RNA-directed DNA methylation induces transcriptional activation in plants

  2009cited by this paper
• Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming

  2009cited by this paper
• Reduced-representation methylation mapping

  2008cited by this paper
• Next-generation DNA sequencing methods.

  2008cited by this paper
• Fixing the front end

  2008cited by this paper
• The methylome: approaches for global DNA methylation profiling.

  2008cited by this paper
• ROS3 is an RNA-binding protein required for DNA demethylation in Arabidopsis

  2008cited by this paper
• Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC) and its application for DNA methylation analysis

  2008cited by this paper
• The sequencing shakeup

  2008cited by this paper
• Highly integrated single-base resolution maps of the epigenome in Arabidopsis.

  2008influential reference
• Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning

  2008influential reference
• A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis

  2008influential reference
• Next-generation DNA sequencing

  2008cited by this paper
• Comprehensive high-throughput arrays for relative methylation (CHARM).

  2008cited by this paper
• Genome-scale DNA methylation maps of pluripotent and differentiated cells

  2008influential reference
• Molecular inversion probe assay.

  2007cited by this paper
• Epigenetic Natural Variation in Arabidopsis thaliana

  2007cited by this paper
• DNA methylation and Sp1 binding determine the tissue-specific transcriptional activity of the mouse Abcc6 promoter.

  2007cited by this paper
• The mammalian epigenome.

  2007cited by this paper
• DNA demethylation in the Arabidopsis genome

  2007influential reference
• Genome-wide in situ exon capture for selective resequencing

  2007cited by this paper
• Direct selection of human genomic loci by microarray hybridization

  2007cited by this paper
• Epigenetic inheritance in plants

  2007cited by this paper
• Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation

  2007cited by this paper
• Cancer epigenomics: DNA methylomes and histone-modification maps

  2007cited by this paper
• Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription

  2007cited by this paper
• The Transcription Factor Nerve Growth Factor-Inducible Protein A Mediates Epigenetic Programming: Altering Epigenetic Marks by Immediate-Early Genes

  2007cited by this paper
• Stability and flexibility of epigenetic gene regulation in mammalian development

  2007cited by this paper
• Genomic patterns of DNA methylation: targets and function of an epigenetic mark.

  2007cited by this paper
• Microarray-based genomic selection for high-throughput resequencing

  2007cited by this paper
• Evidence for an instructive mechanism of de novo methylation in cancer cells

  2006cited by this paper
• DNA methylation regulates long-range gene silencing of an X-linked homeobox gene cluster in a lineage-specific manner.

  2006cited by this paper
• Human embryonic stem cells have a unique epigenetic signature.

  2006cited by this paper
• DNA methylation profiling of human chromosomes 6, 20 and 22

  2006cited by this paper
• G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis

  2006cited by this paper
• Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis.

  2006cited by this paper
• Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3

  2005cited by this paper
• Profiling DNA methylation patterns using genomic tiling microarrays

  2005cited by this paper
• Effects of methylation of non-CpG sequence in the promoter region on the expression of human synaptotagmin XI (syt11).

  2005cited by this paper
• Epigenomic mapping in Arabidopsis using tiling microarrays

  2005cited by this paper
• Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells

  2005cited by this paper
• Eukaryotic cytosine methyltransferases.

  2005cited by this paper
• Direct genomic selection

  2005cited by this paper
• Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis

  2005cited by this paper
• Role of transposable elements in heterochromatin and epigenetic control

  2004cited by this paper
• Epigenetic programming by maternal behavior

  2004cited by this paper
• Maintenance of CpG methylation is essential for epigenetic inheritance during plant gametogenesis

  2003cited by this paper
• Arabidopsis MET1 cytosine methyltransferase mutants.

  2003cited by this paper
• Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation.

  2003cited by this paper
• DNA methylation patterns and epigenetic memory.

  2002cited by this paper
• Role for DNA methylation in the control of cell type–specific maspin expression

  2002cited by this paper
• Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase

  2002cited by this paper
• Role of the arabidopsis DRM methyltransferases in de novo DNA methylation and gene silencing.

  2002cited by this paper
• ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA glycosylase/lyase.

  2002cited by this paper
• Initial sequencing and analysis of the human genome

  2001cited by this paper
• The sequence of the human genome (abstract only)

  2001cited by this paper
• Arabidopsis cmt3 chromomethylase mutations block non-CG methylation and silencing of an endogenous gene.

  2001cited by this paper
• The Sequence of the Human Genome

  2001cited by this paper
• The DNA methyltransferases of mammals.

  2000cited by this paper
• Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene

  2000cited by this paper
• CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus

  2000cited by this paper
• DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.

  1999cited by this paper
• Site-specific DNA methylation in the neurofibromatosis (NF1) promoter interferes with binding of CREB and SP1 transcription factors

  1999cited by this paper
• Transcriptional Regulation of Rat Cyclin D1 Gene by CpG Methylation Status in Promoter Region*

  1999cited by this paper
• Sp1 binding is inhibited by (m)Cp(m)CpG methylation.

  1997cited by this paper
• Sp1 binding is inhibited by mCpmCpG methylation

  1997cited by this paper
• Padlock probes: circularizing oligonucleotides for localized DNA detection.

  1994cited by this paper
• Isolation and identification by sequence homology of a putative cytosine methyltransferase from Arabidopsis thaliana.

  1993cited by this paper
• A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands.

  1992cited by this paper
• The distribution of 5-methylcytosine in the nuclear genome of plants.

  1992cited by this paper
• Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.

  1992cited by this paper
• Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region.

  1991cited by this paper

• Whole-genome DNA methylation analysis of Chinese hamster ovary cells undergoing media adaptation

  2026influential citation
• Integrated epigenomic and transcriptional profiling reveals genotype-specific adaptive reprogramming to drought stress in Brassica napus.

  2026cites this paper
• From genetic code to global health: the impact of nucleic acid vaccines on disease prevention and treatment.

  2025cites this paper
• A pilot multi-omics study reveals genetic mechanisms regulating milk component traits in dairy cattle

  2025cites this paper
• A single-locus quantitative genetic model incorporating DNA methylation.

  2025cites this paper
• Epigenetic foundations of providing support to children left without parental care

  2025cites this paper
• Uncalled4 improves nanopore DNA and RNA modification detection via fast and accurate signal alignment

  2025cites this paper
• The bladder cancer m6A landscape is defined by methylation dilution and 3′-UTR hypermethylation

  2025cites this paper
• Insights into the Molecular Basis of Fruit Development in Prunus Species

  2025cites this paper
• Empowering plant epigenetics to breed resilience of crops: From nucleolar dominance to transgenerational epigenetic inheritance

  2025cites this paper
• Erasing Methylation Marks on DNA by Plant-Specific DEMETER Family DNA Glycosylases

  2024cites this paper
• Uncalled4 improves nanopore DNA and RNA modification detection via fast and accurate signal alignment

  2024cites this paper
• Wemics: A Single‐Base Resolution Methylation Quantification Method for Enhanced Prediction of Epigenetic Regulation

  2024cites this paper
• From Sequencing to Genome Editing in Cucurbitaceae: Application of Modern Genomic Techniques to Enhance Plant Traits

  2024cites this paper
• Expression of genes related to gonadal development and construction of gonadal DNA methylation maps of Trachinotus blochii under hypoxia.

  2024cites this paper
• Global effects of identity and aging on the human sperm methylome

  2023cites this paper
• Synonymous alterations of cancer-associated Trp53 CpG mutational hotspots cause fatal developmental jaw malocclusions but no tumors in knock-in mice

  2023cites this paper
• Genome‐wide impact of cytosine methylation and DNA sequence context on UV‐induced CPD formation

  2023cites this paper
• Herbivory induced methylation changes in the Lombardy poplar: A comparison of results obtained by epiGBS and WGBS

  2023cites this paper
• Epigenetic biomarkers for animal welfare monitoring

  2023cites this paper
• Effects of DNA Methylation on Gene Expression and Phenotypic Traits in Cattle: A Review

  2023cites this paper
• A Critical Analysis of the FDA’s Omics-Driven Pharmacodynamic Biomarkers to Establish Biosimilarity

  2023cites this paper
• Functional genomics in Spiralia

  2023cites this paper
• Current technical advancements in plant epitranscriptomic studies

  2023cites this paper
• Identification of intergenerational epigenetic inheritance by whole genome DNA methylation analysis in trios

  2023cites this paper
• High-throughput Sequencing Technology and Its Application in Epigenetics Studies

  2023cites this paper
• A novel method for predicting DNA N4-methylcytosine sites based on deep forest algorithm

  2023cites this paper
• Efficiently quantifying DNA methylation for bulk- and single-cell bisulfite data

  2023cites this paper
• Re-analysis of publicly available methylomes using signal detection yields new information

  2023cites this paper
• Cytosine epigenetic modifications and conformational changes in G-quadruplex DNA: An ultraviolet resonance Raman spectroscopy study.

  2023cites this paper
• Uncovering plant epigenetics: new insights into cytosine methylation in rye genomes

  2023cites this paper
• Identification of DNA modification sites based on elastic net and bidirectional gated recurrent unit with convolutional neural network

  2022cites this paper
• Environmental DNA analysis for macro-organisms: species distribution and more

  2022cites this paper
• Exploring crucial molecular events in pearl oyster after pre-grafting conditioning by genome-wide bisulfite sequencing for DNA methylation analysis.

  2022cites this paper
• Exploitation of epigenetic variation of crop wild relatives for crop improvement and agrobiodiversity preservation

  2022cites this paper
• Anchor-based bisulfite sequencing determines genome-wide DNA methylation

  2022cites this paper
• Immunomodulatory effects of decitabine in pearl oyster Pinctada fucata martensii.

  2022cites this paper
• Epigenetic variation: A major player in facilitating plant fitness under changing environmental conditions

  2022cites this paper
• Gene expression and epigenetic markers of prion diseases

  2022influential citation
• 5-Formylcytosine weakens the G-C pair and imparts local conformational fluctuations to DNA duplexes.

  2022cites this paper
• Effects of salinity stress on methylation of the liver genome and complement gene in large yellow croaker (Larimichthys crocea).

  2022cites this paper
• Adaptive Divergence without Distinct Species Relationships Indicate Early Stage Ecological Speciation in Species of the Rhododendron pseudochrysanthum Complex Endemic to Taiwan

  2022cites this paper
• DNA Hydroxymethylation in Smoking-Associated Cancers

  2022cites this paper
• MethylSeqLogo: DNA methylation smart sequence logos

  2022cites this paper
• Identification of DNA N4-methylcytosine sites and N6-methyladenine sites 1 through elastic net and bidirectional gated recurrent unit with 2 convolutional neural network

  2022cites this paper
• Modeling dependency structures in 450k DNA methylation data

  2021cites this paper
• DNA Methylation Level Changes in Transgenic Chinese Cabbage (Brassica rapa ssp. pekinensis) Plants and Their Effects on Corresponding Gene Expression Patterns

  2021cites this paper
• DCNN-4mC: Densely connected neural network based N4-methylcytosine site prediction in multiple species

  2021cites this paper
• Distribution, expression and methylation analysis of positively selected genes provides insights into the evolution in Brassica rapa

  2021cites this paper
• Epigenetic Regulation in the Neurogenic Niche of the Adult Dentate Gyrus.

  2021cites this paper
• Stability of DNA methylation and chromatin accessibility in structurally diverse maize genomes

  2021influential citation
• accessibility in

  2021cites this paper
• Diversity of Fungal DNA Methyltransferases and Their Association With DNA Methylation Patterns

  2021cites this paper
• Genome‐wide variation in DNA methylation linked to developmental stage and chromosomal suppression of recombination in white‐throated sparrows

  2021cites this paper
• DNA Modifications: Methods and Protocols

  2021cites this paper
• Mapping DNA Methylation in Mammals: The State of the Art.

  2021cites this paper
• Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells

  2021cites this paper
• Regulation of RNA Methylation by TET Enzymes

  2021cites this paper
• Genetic and Epigenetic Stability in Rye Seeds under Different Storage Conditions: Ageing and Oxygen Effect

  2020cites this paper
• A conformational switch in the zinc finger protein Kaiso mediates differential readout of specific and methylated DNA sequences.

  2020cites this paper
• Regulation of DNA methylation on key parasitism genes of Cysticercus cellulosae revealed by integrative epigenomic-transcriptomic analyses

  2020cites this paper
• Chromatin features define adaptive genomic regions in a fungal plant pathogen

  2020cites this paper
• Genome-wide DNA methylation of the liver reveals delayed effects of early-life exposure to 17-α-ethinylestradiol in the self-fertilizing mangrove rivulus

  2020cites this paper
• Increased accuracy and speed in whole genome bisulfite read mapping using a two-letter alphabet

  2020cites this paper
• A general strategy for highly sensitive analysis of genetic biomarkers at single-base resolution with ligase-based isothermally exponential amplification.

  2020cites this paper
• Fast and memory-efficient mapping of short bisulfite sequencing reads using a two-letter alphabet

  2020cites this paper
• A unique chromatin profile defines adaptive genomic regions in a fungal plant pathogen

  2020cites this paper
• Comprehensive benchmarking of software for mapping whole genome bisulfite data: from read alignment to DNA methylation analysis

  2020cites this paper
• Single-molecule DNA sequencing of widely varying GC-content using nucleotide release, capture and detection in microdroplets

  2020cites this paper
• Genome-Wide Mapping of DNA Methylation 5mC by Methylated DNA Immunoprecipitation (MeDIP)-Sequencing.

  2020cites this paper
• Genome-wide variation in DNA methylation linked to developmental stage and chromosomal suppression of recombination in white-throated sparrows

  2020cites this paper
• Quantum dynamics of the ππ*/nπ* decay of the epigenetic nucleobase 1,5-dimethyl-cytosine in the gas phase.

  2020cites this paper
• Whole-Genome Bisulfite Sequencing and Epigenetic Variation in Cereal Methylomes.

  2020cites this paper
• A cost-effective approach to DNA methylation detection by Methyl Sensitive DArT sequencing

  2020cites this paper
• Advances in whole genome methylomic sequencing

  2020cites this paper
• Cell Lineage Tracing and Cellular Diversity in Humans.

  2020cites this paper
• DNA methylation of the prkaca gene involved in osmoregulation in tilapia hybrids (Oreochromis mossambicus × Oreochromis hornorum).

  2020cites this paper
• DNA methylation methods: global DNA methylation and methylomic analyses.

  2020cites this paper
• DeepTorrent: a deep learning-based approach for predicting DNA N4-methylcytosine sites

  2020cites this paper
• DNA methylation analysis in plants: review of computational tools and future perspectives

  2019cites this paper
• Novel insights into the effects of manipulating DNA methyltransferase levels on the imprinted and non-imprinted regions of the genome

  2019cites this paper
• Dynamic regulation of DNA methylation in human T-cell biology

  2019cites this paper
• Omics: Potential Role in Early Phase Drug Development

  2019cites this paper
• The Role of DNA Methylation in Perennial Plants

  2019influential citation
• Molecular and New-Generation Techniques for Rapid Detection of Foodborne Pathogens and Characterization of Microbial Communities in Poultry Meat

  2019cites this paper
• DNA methylation directs microRNA biogenesis in mammalian cells

  2019cites this paper
• SMaSH: Sample matching using SNPs in humans

  2019cites this paper
• CG dinucleotides enhance promoter activity independent of DNA methylation

  2019cites this paper
• Amphibians as Models for the Study of Cell Proliferation, Differentiation and Apoptosis throughout Embryonic Development and Oviduct Cycles

  2019cites this paper
• Generation of Whole Genome Bisulfite Sequencing Libraries from Very Low DNA Input.

  2019cites this paper
• The influence of DNA methylation on monoallelic expression

  2019cites this paper
• Co-Localization of DNA i-Motif-Forming Sequences and 5-Hydroxymethyl-cytosines in Human Embryonic Stem Cells

  2019cites this paper
• Preliminary Analysis of Within-Sample Co-methylation Patterns in Normal and Cancerous Breast Samples

  2019cites this paper
• Maternal and Post-Weaning High-Fat Diets Produce Distinct DNA Methylation Patterns in Hepatic Metabolic Pathways within Specific Genomic Contexts

  2019cites this paper
• Analysis of epigenetic landscape in a recombinant inbred line population developed by hybridizing natural and re-synthesized Brassica juncea (L.) with stable C-genome introgressions

  2019cites this paper
• Analysis of DNA modifications in aging research

  2018cites this paper
• Nuclear factor I/A coordinates the timing of oligodendrocyte differentiation/maturation via Olig1 promoter methylation

  2018cites this paper
• Global DNA demethylation as an epigenetic marker of human brain metastases

  2018cites this paper
• GENOME-SCALE STUDIES OF DYNAMIC DNA METHYLATION IN MAMMALIAN BRAIN CELLS

  2018cites this paper
• Epigenetic Diversity and Application to Breeding

  2018cites this paper