5-Formylcytosine can be a stable DNA modification in mammals

Bachman, Martin; Uribe-Lewis, Santiago; Yang, Xiaoping; Burgess, Heather E.; Iurlaro, Mario; Reik, Wolf; Murrell, Adele; Balasubramanian, Shankar

doi:10.1038/nchembio.1848

Cited by 239 publications

(225 citation statements)

References 25 publications

Supporting

Mentioning

210

Contrasting

Unclassified

Order By: Relevance

“…The level of 5hmC is known to be a stable mark at high levels in the adult mouse brain (Kinney et al, 2011;Bachman et al, 2014), but relatively very low in embryonic fibroblasts (Kinney et al, 2011). 5fC has been defined as a rare modification found in many tissues (Booth et al, 2014;Bachman et al, 2015), but we have observed that the level of 5fC is higher than that of 5hmC in fibroblasts. Although 5fC is rare, it can exist in specific sites with levels comparable to 5meC and 5hmC (Booth et al, 2014).…”

Section: Discussioncontrasting

confidence: 37%

The sensitivity of 5-formylcytosine to doxorubicin regardless of DNA damage

Uzuner¹,

O’Neill²

2016

Turk J Biol

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 37%

The sensitivity of 5-formylcytosine to doxorubicin regardless of DNA damage

Uzuner¹,

O’Neill²

2016

Turk J Biol

View full text Add to dashboard Cite

show abstract

“…1A) [12,13]. 5hmC, 5fC and 5caC are chemically distinct cytosine modifications that base-pair normally with G and are found at different levels in mammalian genomes [12][13][14][15]. While their individual biological significance is not yet fully understood, the newly discovered 5mC derivatives extend the long-thought binary state of static cytosine modifications to five distinct and possibly dynamic states with yet to be defined epigenetic roles.…”

mentioning

confidence: 94%

“…There is, however, an ongoing debate as to whether the TET-oxidized 5mC derivatives represent DNA demethylation intermediates or have an epigenetic function on their own. In support of an epigenetic function are findings that 5mC derivatives appear to be rather stable in ESCs and tissues (200-6000, 0.2-15 and < 3 ppm total Cs for 5hmC, 5fC and 5caC, respectively) [15,88] and that potential readers can be identified for all of them [92, 93]. Nevertheless, other lines of investigation indicate that the excision of 5fC and 5caC by TDG has functional relevance in ESCs [91].…”

mentioning

confidence: 94%

Active DNA demethylation by DNA repair: Facts and uncertainties

2016

View full text Add to dashboard Cite

Pathways that control and modulate DNA methylation patterning in mammalian cells were poorly understood for a long time, although their importance in establishing and maintaining cell type-specific gene expression was well recognized. The discovery of proteins capable of converting 5-methylcytosine (5mC) to putative substrates for DNA repair introduced a novel and exciting conceptual framework for the investigation and ultimate discovery of molecular mechanisms of DNA demethylation. Against the prevailing notion that DNA methylation is a static epigenetic mark, it turned out to be dynamic and distinct mechanisms appear to have evolved to effect global and locus-specific DNA demethylation. There is compelling evidence that DNA repair, in particular base excision repair, contributes significantly to the turnover of 5mC in cells. By actively demethylating DNA, DNA repair supports the developmental establishment as well as the maintenance of DNA methylation landscapes and gene expression patterns. Yet, while the biochemical pathways are relatively well-established and reviewed, the biological context, function and regulation of DNA repair-mediated active DNA demethylation remains uncertain. In this review, we will thus summarize and critically discuss the evidence that associates active DNA demethylation by DNA repair with specific functional contexts including the DNA methylation erasure in the early embryo, the control of pluripotency and cellular differentiation, the maintenance of cell identity, and the nuclear reprogramming.

show abstract

“…DNA methylation is one of the core epigenetic marks essential for regulating gene expression in normal cell development and differentiation [16]. While 5mC is the most well-characterized, other cytosine modifications have now been discovered, such as 5-hydroxymethycytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) [17,18]. The functions of these exotic marks are still being elucidated, but 5hmC may play an important role in the central nervous system, where it is prevalent, and in the regulation of pluripotency in stem cells [19,20].…”

Section: Epigenetics Overviewmentioning

confidence: 99%

The role of epigenomics in personalized medicine

Kronfol

Dozmorov

Huang

et al. 2017

Expert Review of Precision Medicine and Drug Development

View full text Add to dashboard Cite

Introduction Epigenetics is the study of reversible modifications to chromatin and their extensive and profound effects on gene regulation. To date, the role of epigenetics in personalized medicine has been under-explored. Therefore, this review aims to highlight the vast potential that epigenetics holds. Areas covered We first review the cell-specific nature of epigenetic states and how these can vary with developmental stage and in response to environmental factors. We then summarize epigenetic biomarkers of disease, with a focus on diagnostic tests, followed by a detailed description of current and pipeline drugs with epigenetic modes of action. Finally, we discuss epigenetic biomarkers of drug response. Expert commentary Epigenetic variation can yield information on cellular states and developmental histories in ways that genotype information cannot. Furthermore, in contrast to fixed genome sequence, epigenetic patterns are plastic, so correcting aberrant, disease-causing epigenetic marks holds considerable therapeutic promise. While just six epigenetic drugs are currently approved for use in the United States, a larger number is being developed. However, a drawback to current therapeutics is their non-specific effects. Development of locus-specific epigenetic modifiers, used in conjunction with epigenetic biomarkers of response, will enable truly precision interventions.

show abstract

5-Formylcytosine can be a stable DNA modification in mammals

Cited by 239 publications

References 25 publications

The sensitivity of 5-formylcytosine to doxorubicin regardless of DNA damage

The sensitivity of 5-formylcytosine to doxorubicin regardless of DNA damage

Active DNA demethylation by DNA repair: Facts and uncertainties

The role of epigenomics in personalized medicine

Contact Info

Product

Resources

About