DNA methylation dynamics during the mammalian life cycle

Hackett, Jim; Surani, M. Azim

doi:10.1098/rstb.2011.0328

Cited by 264 publications

(173 citation statements)

References 98 publications

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“…Increasing evidence indicates that, similar to protein-coding genes, epigenetic mechanisms, such as DNA methylation and histone acetylation, may be associated with the regulation of miRNA expression (28). DNA methylation at the dinucleotide CpG is one of the most common epigenetic modifications in eukaryotic genomes and plays a significant role in various biological processes (29). The majority of human miRNA genes have been found to be associated with CpG islands (30).…”

Section: Discussionmentioning

confidence: 99%

Demethylation of microRNA-142 induced by demethylation agents plays a suppressive role in osteosarcoma cells

Ding¹,

Hu²,

Ni³

et al. 2015

Oncology Letters

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Abstract. Osteosarcoma (OS), the most common malignant bone tumor, occurs mainly in adolescents and young adults, with a morbidity of ~5 cases per million. The expression levels of microRNAs (miRNAs) as tumor suppressors were recently found to be downregulated in OS. Certain alterations of miRNAs and the possible mechanisms through which miRNAs affect cell proliferation and migration in OS were recently found to be correlated with methylation epigenetic mechanisms. In this study, it was demonstrated that, due to hypermethylation, the expression level of miRNA-142 (miR-142) was significantly downregulated in OS tissues and cells compared with that in control samples. The present study demonstrated an increased expression of miR-142 in Saos-2 and MG63 cells treated with demethylation agents, suggesting that the effect of such agents on cell growth, inhibition of invasion and cell cycle retardation may be mediated by miR-142 in OS.

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Section: Discussionmentioning

confidence: 99%

Demethylation of microRNA-142 induced by demethylation agents plays a suppressive role in osteosarcoma cells

Ding¹,

Hu²,

Ni³

et al. 2015

Oncology Letters

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“…[9][10][11][12] DNA methylation has been extensively analyzed from a genomic perspective in both normal and pathological tissues, [13][14][15] but the dynamics underlying the methylation and demethylation processes are still not well defined. Several models have addressed these 2 processes by considering the possible influence of the physical distance between CpG sites on these processes.…”

Section: Introductionmentioning

confidence: 99%

Modeling DNA methylation by analyzing the individual configurations of single molecules

et al. 2016

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DNA methylation is often analyzed by reporting the average methylation degree of each cytosine. In this study, we used a single molecule methylation analysis in order to look at the methylation conformation of individual molecules. Using D-aspartate oxidase as a model gene, we performed an in-depth methylation analysis through the developmental stages of 3 different mouse tissues (brain, lung, and gut), where this gene undergoes opposite methylation destiny. This approach allowed us to track both methylation and demethylation processes at high resolution. The complexity of these dynamics was markedly simplified by introducing the concept of methylation classes (MCs), defined as the number of methylated cytosines per molecule, irrespective of their position. The MC concept smooths the stochasticity of the system, allowing a more deterministic description. In this framework, we also propose a mathematical model based on the Markov chain. This model aims to identify the transition probability of a molecule from one MC to another during methylation and demethylation processes. The results of our model suggest that: 1) both processes are ruled by a dominant class of phenomena, namely, the gain or loss of one methyl group at a time; and 2) the probability of a single CpG site becoming methylated or demethylated depends on the methylation status of the whole molecule at that time.

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“…Genome-wide DNA demethylation is observed at two stages of embryonic development, in the fertilized zygote and during the specification of primordial germ cells (PGCs) (9,10). In PGCs, Tet1 and Tet2 contribute to DNA demethylation through a replication-dependent mechanism (9).…”

mentioning

confidence: 99%

Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis

Kang

Lienhard

Pastor

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Dioxygenases of the TET (Ten-Eleven Translocation) family produce oxidized methylcytosines, intermediates in DNA demethylation, as well as new epigenetic marks. Here we show data suggesting that TET proteins maintain the consistency of gene transcription. Embryos lacking Tet1 and Tet3 (Tet1/3 DKO) displayed a strong loss of 5-hydroxymethylcytosine (5hmC) and a concurrent increase in 5-methylcytosine (5mC) at the eight-cell stage. Single cells from eight-cell embryos and individual embryonic day 3.5 blastocysts showed unexpectedly variable gene expression compared with controls, and this variability correlated in blastocysts with variably increased 5mC/5hmC in gene bodies and repetitive elements. Despite the variability, genes encoding regulators of cholesterol biosynthesis were reproducibly down-regulated in Tet1/3 DKO blastocysts, resulting in a characteristic phenotype of holoprosencephaly in the few embryos that survived to later stages. Thus, TET enzymes and DNA cytosine modifications could directly or indirectly modulate transcriptional noise, resulting in the selective susceptibility of certain intracellular pathways to regulation by TET proteins.DNA methylation | cholesterol biosynthesis | TET methylcytosine oxidases | 5-hydroxymethylcytosine | 5hmC

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DNA methylation dynamics during the mammalian life cycle

Cited by 264 publications

References 98 publications

Demethylation of microRNA-142 induced by demethylation agents plays a suppressive role in osteosarcoma cells

Demethylation of microRNA-142 induced by demethylation agents plays a suppressive role in osteosarcoma cells

Modeling DNA methylation by analyzing the individual configurations of single molecules

Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis

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