TET enzymes, TDG and the dynamics of DNA demethylation

By R. Kohli, Yi Zhang. Nature, 2013

1,530 citations recorded by the source corpus.

DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in methyl group removal have remained elusive, until recently. The transformative discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine has greatly advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine is a key nexus in demethylation that can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.

Subfields: Computer Networks and Communications, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/37992ed0adbc69e666cddc5a01b33b884c8d280d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Computer Networks and Communications

1. Hao Wu
2. Yi Zhang

In Molecular Biology

1. Hao Wu
2. Yi Zhang
3. Chuan He
4. Brian D. Strahl
5. Scott B. Rothbart
6. Jianzhao Liu
7. K. Guan
8. Y. Xiong

Citations in the corpus

• Interpreting thelanguage of histone and DNA modifications (2014, background): “Furthermore, fueled in part by the recent discovery of an active DNA demethylation pathway and proteins that read these pathway intermediates [14, 37], a new appreciation for the function of histone PTMs in coordination with DNA modifications is emerging.”
• Mapping and elucidating the function of modified bases in DNA (2017, background): “3).(20) The loss of function of enzymes, including TET and TDG,”
• WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation (2015, positive): “A subsequent decarboxylation of 5caC, by either a thymineDNA glycosylase (TDG) or other DNA repair enzymes, could then lead to DNA demethylation (Kohli and Zhang, 2013).”
• Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, positive): “This mode of active DNA demethylation is distinct from simple passive dilution of 5mC (PD in Figure 2A) (Kohli and Zhang, 2013), as AM-PD may be effective even in the presence of functional methylation maintenance machinery.”
• RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation (2015, background): “Both DNA and histone proteins undergo dynamic and reversible chemical modifications to control gene expression (Strahl and Allis 2000; Bird 2001; Suzuki and Bird 2008; Bhutani et al. 2011; Jones 2012; Kohli and Zhang 2013).”