Emperle M, Bangalore DM, Adam S, Kunert S, Heil HS, Heinze KG, Bashtrykov P, Tessmer I, Jeltsch A (2021)
Publication Type: Journal article
Publication year: 2021
Book Volume: 49
Pages Range: 8294-8308
Journal Issue: 14
DOI: 10.1093/nar/gkab600
DNMT3A/3L heterotetramers contain two active centers binding CpG sites at 12 bp distance, however their interaction with DNA not containing this feature is unclear. Using randomized substrates, we observed preferential co-methylation of CpG sites with 6, 9 and 12 bp spacing by DNMT3A and DNMT3A/3L. Co-methylation was favored by AT bases between the 12 bp spaced CpG sites consistent with their increased bending flexibility. SFM analyses of DNMT3A/3L complexes bound to CpG sites with 12 bp spacing revealed either single heterotetramers inducing 40° DNA bending as observed in the X-ray structure, or two heterotetramers bound side-by-side to the DNA yielding 80° bending. SFM data of DNMT3A/3L bound to CpG sites spaced by 6 and 9 bp revealed binding of two heterotetramers and 100° DNA bending. Modeling showed that for 6 bp distance between CpG sites, two DNMT3A/3L heterotetramers could bind side-by-side on the DNA similarly as for 12 bp distance, but with each CpG bound by a different heterotetramer. For 9 bp spacing our model invokes a tetramer swap of the bound DNA. These additional DNA interaction modes explain how DNMT3A and DNMT3A/3L overcome their structural preference for CpG sites with 12 bp spacing during the methylation of natural DNA.
APA:
Emperle, M., Bangalore, D.M., Adam, S., Kunert, S., Heil, H.S., Heinze, K.G.,... Jeltsch, A. (2021). Structural and biochemical insight into the mechanism of dual CpG site binding and methylation by the DNMT3A DNA methyltransferase. Nucleic Acids Research, 49(14), 8294-8308. https://doi.org/10.1093/nar/gkab600
MLA:
Emperle, Max, et al. "Structural and biochemical insight into the mechanism of dual CpG site binding and methylation by the DNMT3A DNA methyltransferase." Nucleic Acids Research 49.14 (2021): 8294-8308.
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