Active DNA demethylation: many roads lead to Rome

By Susan C. Wu, Yi Zhang. Nature reviews. Molecular cell biology, 2010

1,110 citations recorded by the source corpus.

DNA methylation is one of the best-characterized epigenetic modifications and has been implicated in numerous biological processes, including transposable element silencing, genomic imprinting and X chromosome inactivation. Compared with other epigenetic modifications, DNA methylation is thought to be relatively stable. Despite its role in long-term silencing, DNA methylation is more dynamic than originally thought as active DNA demethylation has been observed during specific stages of development. In the past decade, many enzymes have been proposed to carry out active DNA demethylation and growing evidence suggests that, depending on the context, this process may be achieved by multiple mechanisms. Insight into how DNA methylation is dynamically regulated will broaden our understanding of epigenetic regulation and have great implications in somatic cell reprogramming and regenerative medicine.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f805b1acfc723115408dc05041ce0b9eb454716a

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In Molecular Biology

1. Yi Zhang
2. Hao Wu
3. Peter A. Jones
4. A. Bird
5. S. Baylin
6. Chuan He
7. Wolf Reik
8. Hongjun Song

Citations in the corpus

• Nitric oxide and redox mechanisms in the immune response (2011, background): “Spermine production consumes methylation equivalents, which can reduce the availability of methionine for methylation of DNA and cell proteins [132].”
• Modification of enhancer chromatin: what, how and why? (2013, background): “5hmC has been detected in genomes of several cell types, including ESCs, where it positively correlates with gene activity and is found at promoters, gene bodies, and enhancers (Ficz et al., 2011; Pastor et al., 2011; Stroud et al., 2011; Szulwach et al., 2011; Valinluck et al., 2004; Wu and Zhang, ”
• Neuronal activity modifies DNA methylation landscape in the adult brain (2011, background): “In contrast to readily reversible histone modifications, DNA methylation has been generally regarded as a highly stable epigenetic mark in differentiated cells to ensure transcriptional gene silencing and maintain cell type identit”
• DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos (2014, background): “Instead, several alternative, active demethylation mechanisms that are passive and indirect have been proposed and demonstrated (Wu and Zhang 2014, 2010).”
• Uncovering the role of 5-hydroxymethylcytosine in the epigenome (2011, background): “Is 5hmC a demethylation intermediate? Several mechanisms for the removal of 5mC have been propose”
• TET-mediated active DNA demethylation: mechanism, function and beyond (2017, background): “TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23).”
• Tissue Distribution of 5-Hydroxymethylcytosine and Search for Active Demethylation Intermediates (2010, background): “During preparation of this manuscript a review was published, which independently postulated these two putative pathways for active DNA demethylation [24].”
• CpG islands and the regulation of transcription. (2011, positive): “An alternative possibility is that methylation at CGIs is actively removed by a DNA demethylase (Wu and Zhang 2010), but uncertainty concerning the identity of the DNA demethylating activities in animals has made this hypothesis difficult to test.”
• Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine (2010, background): “It is possible that conversion of 5-mC to 5-hmC is a pathway to offset the gene repression effect of 5-mC during this process without going through demethylatio”
• Thymine DNA Glycosylase Is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair (2011, neutral): “Indeed, it has been controversial as to whether demethylation is an active process in mammals (Ooi and Bestor, 2008) and which mechanisms are involved (Wu and Zhang, 2010).”
• Epigenetic Modifications as Therapeutic Targets (2010, background): “, mainly in embryonic stem cells and Purkinje cell”
• Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation (2010, background): “Although the physiological significance of 5-OH-MeC remains to be determined, it is likely to be the intermediate in the pathway that actively demethylates 5-methylcytosine (Wu and Zhang, 2010).”