Dynamic<i>Alu</i>Methylation during Normal Development, Aging, and Tumorigenesis

Luo, Ye; Lu, Xuemei; Xie, Hehuang

doi:10.1155/2014/784706

Cited by 78 publications

(69 citation statements)

References 143 publications

(155 reference statements)

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“…Besides the common methylated state of Alu repeats and the well-established global demethylation in cancer and aging (Esteller 2008;Ehrlich 2009), multiple studies have unveiled physiological and pathological irregularities in the methylation pattern of specific Alu elements (Hellmann-Blumberg et al 1993;Brohede and Rand 2006;Rodriguez et al 2008b;Rand and Molloy 2010;Luo et al 2014). There is a vast repertoire of methodologies to analyze DNA methylation (Esteller 2007;Beck 2010;Gu et al 2010;Jordà and Peinado 2010;Laird 2010;Stirzaker et al 2014), and different approaches have been used to make bulk estimates of methylation in repetitive elements (Yang et al 2004;Weisenberger et al 2005;Choi et al 2007;Jintaridth and Mutirangura 2010;Xiang et al 2010;Wu et al 2011;Yoshida et al 2011;Gilson and Horard 2012;Buj et al 2016).…”

Section: Discussion Technical Considerationsmentioning

confidence: 99%

“…Several authors have proposed that Alu elements may act as a large reservoir of functional complexity, constituting alternative mechanisms involved in the assembly and evolution of regulatory networks. Acquired regulatory properties of Alu repeats include the generation of novel transcription factor binding sites, transcriptional regulation of some novel miRNAs, alternative splicing, and gene silencing, among others (Cordaux and Batzer 2009;Keren et al 2010;Ichiyanagi 2013;Luo et al 2014).…”

Section: Individual Features Of Unmethylated Alu Repeats and Functionmentioning

confidence: 99%

“…Alu elements are the most abundant repeat, with more than 1 million copies per haploid genome and spanning ∼10% of the genome sequence (Cordaux and Batzer 2009). Alu repeats tend to accumulate in gene-rich regions (International Human Genome Sequencing Consortium 2001;Chen et al 2002;Grover et al 2004) and harbor ∼25% of all CpG dinucleotides in the human genome (Luo et al 2014;Buj et al 2016). On the other hand, LINEs, which are depleted in gene-rich regions and span 20% of the human genome, contain ∼12% of the methylated cytosines (Xie et al 2009;Luo et al 2014;Buj et al 2016).…”

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confidence: 99%

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The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells

et al. 2016

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Cancer cells exhibit multiple epigenetic changes with prominent local DNA hypermethylation and widespread hypomethylation affecting large chromosomal domains. Epigenome studies often disregard the study of repeat elements owing to technical complexity and their undefined role in genome regulation. We have developed NSUMA (Next-generation Sequencing of UnMethylated Alu), a cost-effective approach allowing the unambiguous interrogation of DNA methylation in more than 130,000 individual Alu elements, the most abundant retrotransposon in the human genome. DNA methylation profiles of Alu repeats have been analyzed in colon cancers and normal tissues using NSUMA and whole-genome bisulfite sequencing. Normal cells show a low proportion of unmethylated Alu (1%-4%) that may increase up to 10-fold in cancer cells. In normal cells, unmethylated Alu elements tend to locate in the vicinity of functionally rich regions and display epigenetic features consistent with a direct impact on genome regulation. In cancer cells, Alu repeats are more resistant to hypomethylation than other retroelements. Genome segmentation based on high/low rates of Alu hypomethylation allows the identification of genomic compartments with differential genetic, epigenetic, and transcriptomic features. Alu hypomethylated regions show low transcriptional activity, late DNA replication, and its extent is associated with higher chromosomal instability. Our analysis demonstrates that Alu retroelements contribute to define the epigenetic landscape of normal and cancer cells and provides a unique resource on the epigenetic dynamics of a principal, but largely unexplored, component of the primate genome.

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Section: Discussion Technical Considerationsmentioning

confidence: 99%

Section: Individual Features Of Unmethylated Alu Repeats and Functionmentioning

confidence: 99%

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confidence: 99%

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The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells

et al. 2016

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“…CpG sites within repetitive elements such as L1 and Alu are normally hypermethylated to prevent their expression. Especially, Alu repeats tend to accumulate in gene-rich regions and span roughly one quarter of all CpG dinucleotides in the human genome [63][64][65]. datasets, again indicating that no consistent technical variation was introduced during processing of the saliva samples.…”

Section: Comparable Dna Methylation Patterns Between Blood and Salivamentioning

confidence: 99%

Saliva as a Blood Alternative for Genome-Wide DNA Methylation Profiling by Methylated DNA Immunoprecipitation (MeDIP) Sequencing

et al. 2017

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Abstract:Background: Interrogation of DNA methylation profiles hold promise for improved diagnostics, as well as the delineation of the aetiology for common human diseases. However, as the primary tissue of the disease is often inaccessible without complicated and inconvenient interventions, there is an increasing interest in peripheral surrogate tissues. Whereas most work has been conducted on blood, saliva is now becoming recognized as an interesting alternative due to the simple and non-invasive manner of collection allowing for self-sampling. Results: In this study we have evaluated if saliva samples are suitable for DNA methylation studies using methylated DNA immunoprecipitation coupled to next-generation sequencing (MeDIP-seq). This was done by comparing the DNA methylation profile in saliva against the benchmark profile of peripheral blood from three individuals. We show that the output, quality, and depth of paired-end 50 bp sequencing reads are comparable between saliva and peripheral blood and, moreover, that the distribution of reads along genomic regions are similar and follow canonical methylation patterns. Conclusion: In summary, we show that high-quality MeDIP-seq data can be generated using saliva, thus supporting the future use of saliva in the generation of DNA methylation information at annotated genes, non-RefSeq genes, and repetitive elements relevant to human disease.

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“…The correct DNA methylation patterns provide regulation of cell type-specific gene expression by affecting the capacity of DNA to interact with transcription factors and methyl-CpG-binding proteins (Doerfler 1981, Razin & Cedar 1991, Zou et al 2012). Numerous studies discuss the possible role of the altered DNA methylation patterns in the initiation and progression of various pathologies, including developmental failures (Shi & Haaf 2002, Pliushch et al 2010, Ehrlich & Lacey 2013, Shubina et al 2013, Skryabin et al 2013, Zheleznyakova et al 2013, Luo et al 2014, Pendina et al 2014.…”

Section: Introductionmentioning

confidence: 99%

Chromosome hydroxymethylation patterns in human zygotes and cleavage-stage embryos

Efimova¹,

Pendina²,

Tikhonov³

et al. 2015

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We report the sequential changes in 5-hydroxymethylcytosine (5hmC) patterns in the genome of human preimplantation embryos during DNA methylation reprogramming. We have studied chromosome hydroxymethylation and methylation patterns in triploid zygotes and blastomeres of cleavage-stage embryos. Using indirect immunofluorescence, we have analyzed the localization of 5hmC and its co-distribution with 5-methylcytosine (5mC) on the QFH-banded metaphase chromosomes. In zygotes, 5hmC accumulates in both parental chromosome sets, but hydroxymethylation is more intensive in the poorly methylated paternal set. In the maternal set, chromosomes are highly methylated, but contain little 5hmC. Hydroxymethylation is highly region specific in both parental chromosome sets: hydroxymethylated loci correspond to R-bands, but not G-bands, and have well-defined borders, which coincide with the R/G-band boundaries. The centromeric regions and heterochromatin at 1q12, 9q12, 16q11.2, and Yq12 contain little 5mC and no 5hmC. We hypothesize that 5hmC may mark structural/functional genome 'units' corresponding to chromosome bands in the newly formed zygotic genome. In addition, we suggest that the hydroxymethylation of R-bands in zygotes can be treated as a new characteristic distinguishing them from G-bands. At cleavages, chromosomes with asymmetrical hydroxymethylation of sister chromatids appear. They decrease in number during cleavages, whereas totally non-hydroxymethylated chromosomes become numerous. Taken together, our findings suggest that, in the zygotic genome, 5hmC is distributed selectively and its pattern is determined by both parental origin of chromosomes and type of chromosome bands -R, G, or C. At cleavages, chromosome hydroxymethylation pattern is dynamically changed due to passive and non-selective overall loss of 5hmC, which coincides with that of 5mC.

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DynamicAluMethylation during Normal Development, Aging, and Tumorigenesis

Cited by 78 publications

References 143 publications

The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells

The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells

Saliva as a Blood Alternative for Genome-Wide DNA Methylation Profiling by Methylated DNA Immunoprecipitation (MeDIP) Sequencing

Chromosome hydroxymethylation patterns in human zygotes and cleavage-stage embryos

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