Molecular coupling of DNA methylation and histone methylation
- PMID: 21339843
- PMCID: PMC3039846
- DOI: 10.2217/epi.10.44
Molecular coupling of DNA methylation and histone methylation
Abstract
The combinatorial pattern of DNA and histone modifications constitutes an epigenetic 'code' that shapes gene-expression patterns by enabling or restricting the transcriptional potential of genomic domains. DNA methylation is associated with histone modifications, particularly the absence of histone H3 lysine 4 methylation (H3K4me0) and the presence of H3K9 methylation. This article focuses on three protein domains (ATRX-Dnmt3-Dnmt3L [ADD], Cys-X-X-Cys [CXXC] and the methyl-CpG-binding domain [MBD]) and the functional implications of domain architecture in the mechanisms linking histone methylation and DNA methylation in mammalian cells. The DNA methyltransferase DNMT3a and its accessory protein Dnmt 3L contain a H3K4me0-interacting ADD domain that links the DNA methylation reaction with unmodified H3K4. The H3K4 methyltransferase MLL1 contains a CpG-interacting CXXC domain that may couple the H3K4 methylation reaction to unmethylated DNA. Another H3K4 methyltransferase, SET1, although lacking an intrinsic CXXC domain, interacts directly with an accessory protein CFP1 that contains the same domain. The H3K9 methyltransferase SETDB1 contains a putative MBD that potentially links the H3K4 methylation reaction to methylated DNA or may do so through the interaction with the MBD containing protein MBD1. Finally, we consider the domain structure of the DNA methyltransferase DNMT1, its accessory protein UHRF1 and their associated proteins, and propose a mechanism by which DNA methylation and histone methylation may be coordinately maintained through mitotic cell division, allowing for the transmission of parental DNA and for the histone methylation patterns to be copied to newly replicated chromatin.
Keywords: ADD; CXXC; CpG-binding domain; H3K4me0-binding domain; MBD; SRA; hemi-methyl-CpG-binding domain; methyl-CpG-binding domain.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3039846/bin/nihms268522f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3039846/bin/nihms268522f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3039846/bin/nihms268522f3.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3039846/bin/nihms268522f4.gif)
Similar articles
-
Functional specificity of CpG DNA-binding CXXC domains in mixed lineage leukemia.J Biol Chem. 2013 Oct 11;288(41):29901-10. doi: 10.1074/jbc.M113.474858. Epub 2013 Aug 29. J Biol Chem. 2013. PMID: 23990460 Free PMC article.
-
Introduction--Epiphanies in epigenetics.Prog Mol Biol Transl Sci. 2011;101:1-21. doi: 10.1016/B978-0-12-387685-0.00001-9. Prog Mol Biol Transl Sci. 2011. PMID: 21507348 Free PMC article.
-
Structural insight into autoinhibition and histone H3-induced activation of DNMT3A.Nature. 2015 Jan 29;517(7536):640-4. doi: 10.1038/nature13899. Epub 2014 Nov 10. Nature. 2015. PMID: 25383530
-
Regulation of maintenance DNA methylation via histone ubiquitylation.J Biochem. 2016 Jan;159(1):9-15. doi: 10.1093/jb/mvv113. Epub 2015 Nov 20. J Biochem. 2016. PMID: 26590302 Free PMC article. Review.
-
ZF-CxxC domain-containing proteins, CpG islands and the chromatin connection.Biochem Soc Trans. 2013 Jun;41(3):727-40. doi: 10.1042/BST20130028. Biochem Soc Trans. 2013. PMID: 23697932 Free PMC article. Review.
Cited by
-
Umbilical Cord Blood-Derived Cells Can Reconstruct Hematopoiesis in an Aplastic Anemia Animal Model.Stem Cells Int. 2024 Aug 12;2024:4095268. doi: 10.1155/2024/4095268. eCollection 2024. Stem Cells Int. 2024. PMID: 39161367 Free PMC article.
-
Evaluating the Role of Neddylation Modifications in Kidney Renal Clear Cell Carcinoma: An Integrated Approach Using Bioinformatics, MLN4924 Dosing Experiments, and RNA Sequencing.Pharmaceuticals (Basel). 2024 May 15;17(5):635. doi: 10.3390/ph17050635. Pharmaceuticals (Basel). 2024. PMID: 38794205 Free PMC article.
-
Emerging Roles of Vitamin B12 in Aging and Inflammation.Int J Mol Sci. 2024 May 6;25(9):5044. doi: 10.3390/ijms25095044. Int J Mol Sci. 2024. PMID: 38732262 Free PMC article. Review.
-
Structural insights into the binding mechanism of Clr4 methyltransferase to H3K9 methylated nucleosome.Sci Rep. 2024 Mar 5;14(1):5438. doi: 10.1038/s41598-024-56248-2. Sci Rep. 2024. PMID: 38443490 Free PMC article.
-
Metabolic memory: mechanisms and diseases.Signal Transduct Target Ther. 2024 Feb 28;9(1):38. doi: 10.1038/s41392-024-01755-x. Signal Transduct Target Ther. 2024. PMID: 38413567 Free PMC article. Review.
References
-
- Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403:41–45. - PubMed
-
- Probst AV, Dunleavy E, Almouzni G. Epigenetic inheritance during the cell cycle. Nat Rev Mol Cell Biol. 2009;10:192–206. - PubMed
-
- Barreto G, Schäfer A, Marhold J, et al. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature. 2007;445:671–675. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials