De novo methylation of nucleosomal DNA by the mammalian Dnmt1 and Dnmt3A DNA methyltransferases
- PMID: 16026162
- DOI: 10.1021/bi047634t
De novo methylation of nucleosomal DNA by the mammalian Dnmt1 and Dnmt3A DNA methyltransferases
Abstract
In the cell, DNA is wrapped on histone octamers, which reduces its accessibility for DNA interacting enzymes. We investigated de novo methylation of nucleosomal DNA in vitro and show that the Dnmt3a and Dnmt1 DNA methyltransferases efficiently methylate nucleosomal DNA without dissociation of the histone octamer from the DNA. In contrast, the prokaryotic SssI DNA methyltransferase and the catalytic domain of Dnmt3a are strongly inhibited by nucleosomes. We also found that full-length Dnmt1 and Dnmt3a bind to nucleosomes much stronger than their isolated catalytic domains, demonstrating that the N-terminal parts of the MTases are required for the interaction with nucleosomes. Variations of the DNA sequence or the histone tails did not significantly influence the methylation activity of Dnmt3a. The observation that mammalian methyltransferases directly modify nucleosomal DNA provides an insight into the mechanisms by which histone tail and DNA methylation patterns can influence each other because the DNA methylation pattern can be established while histones remain associated to the DNA.
Similar articles
-
Mouse Dnmt3a preferentially methylates linker DNA and is inhibited by histone H1.J Mol Biol. 2008 Nov 21;383(4):810-21. doi: 10.1016/j.jmb.2008.03.001. Epub 2008 Mar 8. J Mol Biol. 2008. PMID: 18823905
-
Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked and nucleosomal DNA.J Biochem. 2006 Mar;139(3):503-15. doi: 10.1093/jb/mvj044. J Biochem. 2006. PMID: 16567415
-
The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.J Mol Biol. 2001 Jun 22;309(5):1189-99. doi: 10.1006/jmbi.2001.4709. J Mol Biol. 2001. PMID: 11399088
-
Structure and function of mammalian DNA methyltransferases.Chembiochem. 2011 Jan 24;12(2):206-22. doi: 10.1002/cbic.201000195. Epub 2010 Nov 29. Chembiochem. 2011. PMID: 21243710 Review.
-
Regulation of expression and activity of DNA (cytosine-5) methyltransferases in mammalian cells.Prog Mol Biol Transl Sci. 2011;101:311-33. doi: 10.1016/B978-0-12-387685-0.00009-3. Prog Mol Biol Transl Sci. 2011. PMID: 21507356 Review.
Cited by
-
Characterization of Dnmt1 Binding and DNA Methylation on Nucleosomes and Nucleosomal Arrays.PLoS One. 2015 Oct 23;10(10):e0140076. doi: 10.1371/journal.pone.0140076. eCollection 2015. PLoS One. 2015. PMID: 26496704 Free PMC article.
-
Rethinking how DNA methylation patterns are maintained.Nat Rev Genet. 2009 Nov;10(11):805-11. doi: 10.1038/nrg2651. Epub 2009 Sep 30. Nat Rev Genet. 2009. PMID: 19789556 Free PMC article. Review.
-
CGGBP1 mitigates cytosine methylation at repetitive DNA sequences.BMC Genomics. 2015 May 16;16(1):390. doi: 10.1186/s12864-015-1593-2. BMC Genomics. 2015. PMID: 25981527 Free PMC article.
-
DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes.Oncogene. 2013 Nov 21;32(47):5421-8. doi: 10.1038/onc.2013.162. Epub 2013 May 20. Oncogene. 2013. PMID: 23686312 Free PMC article.
-
Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation.Nucleic Acids Res. 2007;35(13):4301-12. doi: 10.1093/nar/gkm432. Epub 2007 Jun 18. Nucleic Acids Res. 2007. PMID: 17576694 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
