5-Hydroxymethylcytosine Profiling as an Indicator of Cellular State

Abstract

DNA methylation is widely studied in the context of cancer. However, the rediscovery of 5-hydroxymethylation of DNA adds a new layer of complexity to understanding the epigenetic basis of development and disease, including carcinogenesis. There have been significant advances in techniques for the detection of 5-hydroxymethylcytosine and, with this, greater insight into the distribution, regulation and function of this mark, which are reviewed here. Better understanding of the associated pathways involved in regulation of, and by, 5-hydroxymethylcytosine may give promise to new therapeutic targets. We discuss evidence to support the view of 5-hydroxymethylcytosine as a unique and dynamic mark of cellular state. These 5-hydroxymethylcytosine profiles may offer optimism for the development of diagnostic, prognostic and predictive biomarkers.

Epigenetic Changes and Functional Study of HOXA11 in Human Gastric Cancer

“…In addition to 5mC (5-methylcytosine), reduction in 5hmC (5-hydroxymethylcytosine) was well reported in a number of cancers and cell lines corresponding to prostate, breast, colon, lung, brain, liver, kidney and melanoma, compared with the associated normal tissue [37][38][39][40][41]. But the level of 5hmC is highly variable and unreproducible [39,42].…”

“…But the level of 5hmC is highly variable and unreproducible [39,42]. It was undetectable in some human cancer tissues and cells [43].…”

Whole-genome analysis of the methylome and hydroxymethylome in normal and malignant lung and liver

“…DNA methylation is an important epigenetic modification that plays a role in diverse biological processes, including maintenance of genomic stability, gene silencing, embryonic development, and tumorigenesis (Jones 2012;Smith and Meissner 2013;Timp and Feinberg 2013). Recently, a family of ten-eleven translocation methylcytosine dioxygenase (TET) proteins was shown to oxidize 5mC (5-methylcytosine) to 5hmC (5-hydroxymethylcytosine) (Laird et al 2013;Wu and Zhang 2014). TET-mediated 5hmC is abundant in a variety of mammalian tissues, such as brain and stem cells (Pastor et al 2013), and plays a role in epigenetic reprogramming, cell differentiation, and tumorigenesis.…”

“…Several strategies have been developed to label and enrich 5hmC, followed by sequencing with limited resolution (Laird et al 2013;Putiri et al 2014). Recently, two methods were implemented allowing for quantification of 5hmC at a single-base resolution.…”

Epigenetically modified nucleotides in chronic heroin and cocaine treated mice

“…The global levels of 5-hmC have been recently used to evaluate the effectiveness of anticancer agents (Laird et al, 2013). Furthermore, a global increase in 5-hmC levels in the cartilage of patients suffering from osteoarthritis, compared to normal tissue, was reported (Taylor et al, 2014).…”