A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters

Saxonov, Serge; Berg, Paul; Brutlag, Douglas L.

doi:10.1073/pnas.0510310103

Cited by 1,152 publications

(974 citation statements)

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“…For the genomic feature comparisons, CpGs from nascent or bulk DNA were intersected using BedTools v2.25.0 with: CpG islands, as previously defined in Ref 43 , H1-specific typical or super-enhancers, exons, introns, high CpG density or low CpG density promoters (Ref 44 ), Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs) downloaded from the UCSC Genome Browser. H3K27me3, H3K4me3, H3K27ac and EZH2 annotations were downloaded for H1 ESCs from UCSC.…”

Section: Methodsmentioning

confidence: 99%

Global delay in nascent strand DNA methylation

Charlton

Downing

Smith

et al. 2018

Nat Struct Mol Biol

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Cytosine methylation is widespread among organisms and essential for mammalian development. In line with early postulations of an epigenetic role in gene regulation, symmetric CpG methylation can be mitotically propagated over many generations with extraordinarily high fidelity. Here, we combine BrdU labeling and immunoprecipitation with genome-wide bisulfite sequencing to explore the inheritance of cytosine methylation onto newly replicated DNA in human cells. Globally, we observe a pronounced lag between the copying of genetic and epigenetic information that is reconsolidated within hours to accomplish faithful mitotic transmission. Populations of arrested cells show a global reduction of lag induced intermediate CpG methylation when compared to proliferating cells, while sites of transcription factor engagement appear cell-cycle invariant. Alternatively, the cancer cell line HCT116 preserves global epigenetic heterogeneity independently of cell-cycle arrest. Taken together, our data suggest that heterogeneous methylation largely reflects asynchronous proliferation, but is intrinsic to actively engaged cis-regulatory elements and cancer.

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Section: Methodsmentioning

confidence: 99%

Global delay in nascent strand DNA methylation

Charlton

Downing

Smith

et al. 2018

Nat Struct Mol Biol

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“…As most CpGs are located outside of CpG islands and are highly methylated, this translates to an overall loss of DNA methylation in later life as well as a tendency for DNA methylation levels to shift toward the mean with increased age (Saxonov et al ., 2006; Weber et al ., 2007; Illingworth & Bird, 2009; Hannum et al ., 2013; Teschendorff et al ., 2013; Weidner et al ., 2014). …”

Section: Dna Methylation Dynamics During Agingmentioning

confidence: 99%

“…This balance of responsiveness to stimuli and heritability results in a unique mechanism for lasting signatures of prior exposures that accumulate over the lifetime (Cortessis et al ., 2012; Feil & Fraga, 2012). As an example of a specific exposure that has been shown to leave a lasting signature, cigarette smoke has been linked to changes in DNA methylation at the AHRR locus both in smokers and in children of smokers (Saxonov et al ., 2006; Monick et al ., 2012; Joubert et al ., 2012; Shenker et al ., 2013; Sun et al ., 2013 Elliott et al ., 2014; Lee et al ., 2015; Shah et al ., 2014). Smoking‐associated DNA methylation changes have also been found in genes involved in inflammatory networks, important candidates in the risk of age‐related diseases such as heart disease and stroke (Breitling et al ., 2012; Dogan et al ., 2014).…”

Section: Epigenetic Drift Vs the Epigenetic Clock: Two Phenomena Undmentioning

confidence: 99%

“…The most common form of DNA methylation involves the addition of a methyl group to the 5′ cytosine of C‐G dinucleotides, referred to as CpGs. These nucleotide pairs are relatively sparse in the genome, and areas of comparatively high CpG density are referred to as CpG islands, identified as regions > 200 bp with a > 50% G+C content and 0.6 observed/expected ratio of CpGs (Saxonov et al ., 2006; Illingworth & Bird, 2009). These islands tend to be less methylated compared to nonisland CpGs and are often associated with gene promoters, while the regions immediately surrounding CpG islands are referred to as ‘shores’, followed by ‘shelves’.…”

Section: Introductionmentioning

confidence: 99%

“…These islands tend to be less methylated compared to nonisland CpGs and are often associated with gene promoters, while the regions immediately surrounding CpG islands are referred to as ‘shores’, followed by ‘shelves’. Approximately 60–70% of genes have a CpG island associated with their promoters, and promoters can be classified according to their CpG density (Saxonov et al ., 2006; Weber et al ., 2007). Levels of DNA methylation at a promoter‐associated CpG island are generally negatively associated with gene expression, although some specific genes show the opposite effect (Weber et al ., 2007; Lam et al ., 2012; Gutierrez Arcelus et al ., 2013).…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation and healthy human aging

2015

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SummaryThe process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next‐generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site‐specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age‐related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining ‘epigenetic age’ for human health and outline some important caveats to existing and future studies.

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Monozygotic Twins and Epigenetics

Doucet

Wong

2012

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters

Cited by 1,152 publications

References 47 publications

Global delay in nascent strand DNA methylation

Global delay in nascent strand DNA methylation

DNA methylation and healthy human aging

Monozygotic Twins and Epigenetics

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