Abstract
The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine—5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine—have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine—N4-methylcytosine and N6-methyladenine—are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified bases from prokaryotes and eukaryotes. Despite significant differences in structures and functions, they are remarkably similar regarding their engagement in flipping a target base/nucleotide within DNA for specific recognitions and/or reactions. We thus highlight base flipping as a common structural framework broadly applied by distinct classes of proteins and enzymes across phyla for epigenetic regulations of DNA.
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Abbreviations
- 5caC:
-
5-Carboxylcytosine
- 5fC:
-
5-Formylcytosine
- 5ghmC:
-
Glucosylated 5-hydroxymethylcytosine
- 5hmC:
-
5-Hydroxymethylcytosine
- 5mC:
-
5-Methylcytosine
- AdoHcy:
-
S-Adenosyl-l-homocysteine
- AdoMet:
-
S-Adenosyl-l-methionine
- AlkB:
-
E. coli alkylated DNA repair protein
- ALKBH5:
-
Alkylated DNA repair protein AlkB homolog 5 in human
- CMT2:
-
Chromomethylase 2 (plant specific)
- CMT3:
-
Chromomethylase 3 (plant specific)
- DME:
-
Demeter (plant)
- DML3:
-
Demeter-like protein 3 (plant)
- DNMT1:
-
Mammalian DNA methyltransferase 1
- DNMT3A:
-
Mammalian DNA methyltransferase 3A
- DNMT3L:
-
Mammalian DNA methyltransferase 3-like
- DRM2:
-
Domain rearranged methyltransferase 2 (plant)
- FTO:
-
Fat mass and obesity-associated protein
- HhH:
-
Helix-hairpin-helix
- JBP:
-
J-binding protein
- MBD:
-
Methyl-CpG-binding domain
- McrB:
-
Modified cytosine restriction B
- Met1:
-
DNA methyltransferase 1 (plant)
- MTase:
-
Methyltransferase
- N4mC:
-
N4-methylcytosine
- N6mA:
-
N6-methyladenine
- NOG:
-
N-oxalylglycine
- ROS1:
-
Repressor of silencing 1 (plant specific)
- SRA:
-
SET and RING associated
- TDG:
-
Thymine DNA glycosylase
- TET:
-
Ten-eleven translocation
- TRD:
-
Target recognition domain
- Uhrf1:
-
Ubiquitin-like-containing PHD and RING finger domains protein 1
- WH:
-
Winged helix
- αKG:
-
α-Ketoglutarate
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Acknowledgments
The work in the authors’ laboratory is supported by grant from National Institutes of Health (GM049245-22). X.C. is a Georgia Research Alliance Eminent Scholar.
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Hong, S., Cheng, X. (2016). DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications. In: Jeltsch, A., Jurkowska, R. (eds) DNA Methyltransferases - Role and Function. Advances in Experimental Medicine and Biology, vol 945. Springer, Cham. https://doi.org/10.1007/978-3-319-43624-1_14
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