The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation
Open accessAbstract
Cytosine residues in mammalian DNA occur in at least three forms, cytosine (C), 5-methylcytosine (M; 5mC) and 5-hydroxymethylcytosine (H; 5hmC). During semi-conservative DNA replication, hemi-methylated (M/C) and hemi-hydroxymethylated (H/C) CpG dinucleotides are transiently generated, where only the parental strand is modified and the daughter strand contains native cytosine. Here, we explore the role of DNA methyltransferases (DNMT) and ten eleven translocation (Tet) proteins in perpetuating these states after replication, and the molecular basis of their recognition by methyl-CpG-binding domain (MBD) proteins. Using recombinant proteins and modified double-stranded deoxyoligonucleotides, we show that DNMT1 prefers a hemi-methylated (M/C) substrate (by a factor of >60) over hemi-hydroxymethylated (H/C) and unmodified (C/C) sites, whereas both DNMT3A and DNMT3B have approximately equal activity on all three substrates (C/C, M/C and H/C). Binding of MBD proteins to methylated DNA inhibited Tet1 activity, suggesting that MBD binding may also play a role in regulating the levels of 5hmC. All five MBD proteins generally have reduced binding affinity for 5hmC relative to 5mC in the fully modified context (H/M versus M/M), though their relative abilities to distinguish the two varied considerably. We further show that the deamination product of 5hmC could be excised by thymine DNA glycosylase and MBD4 glycosylases regardless of context.
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Citations
Cites
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality
Li, E., Bestor, T. H., & Jaenisch, R. (1992) · Cell · doi:10.1016/0092-8674(92)90611-f · Cited by 3,984
The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
Kriaucionis, S., & Heintz, N. (2009) · Science · doi:10.1126/science.1169786 · Cited by 2,700
Jin, S.-G., Kadam, S., & Pfeifer, G. P. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq223 · Cited by 437
Gnanapragasam, M. N., Scarsdale, J. N., Amaya, M. L., Webb, H. D., Desai, M. A., Walavalkar, N. M., Wang, S. Z., Zu Zhu, S., Ginder, G. D., & Williams, D. C. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015341108 · Cited by 148
Sharma, S., De Carvalho, D. D., Jeong, S., Jones, P. A., & Liang, G. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001286 · Cited by 119
Cited by
DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045
TET-mediated active DNA demethylation: mechanism, function and beyond
Wu, X., & Zhang, Y. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.33 · Cited by 1,661
Krokan, H. E., & Bjoras, M. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012583 · Cited by 1,322
Role of TET enzymes in DNA methylation, development, and cancer
Rasmussen, K. D., & Helin, K. (2016) · Genes & Development · doi:10.1101/gad.276568.115 · Cited by 1,040
“2003; Jones and Liang 2009), and these enzymes readily methylate a DNA substrate containing 5hmC (Hashimoto et al. 2012; Ji et al. 2014).”
BackgroundInfluentialReversing DNA Methylation: Mechanisms, Genomics, and Biological Functions
Wu, H., & Zhang, Y. (2014) · Cell · doi:10.1016/j.cell.2013.12.019 · Cited by 1,065
“While there are conflicting results regarding whether UHRF1 can efficiently recognize hemihydroxymethylated CpG sites (hCG:GC) (Frauer et al., 2011; Hashimoto et al., 2012), independent studies have established that DNMT1 is significantly less efficient (10 60- fold) in methylating hCG:GC than…”
Influential
Metadata
- Authors
- Hashimoto, H., Liu, Y., Upadhyay, A. K., Chang, Y., Howerton, S. B., Vertino, P. M., Zhang, X., & Cheng, X.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-02-22
- Volume
- 40
- Issue
- 11
- Pages
- 4841-4849
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2046812959
- Cited by
- 477
- References
- 5
- FWCI
- 17.77
- Type
- journal article
- Language
- en
- Open access
- gold
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