Abstract
Covalent modification of DNA via deposition of a methyl group at the 5′ position on cytosine residues alters the chemical groups available for interaction in the major groove of DNA. This modification, thereby, alters the affinity and specificity of DNA-binding proteins; some of them favor interaction with methylated DNA, and others disfavor it. Molecular recognition of cytosine methylation by proteins often initiates sequential regulatory events that impact gene expression and chromatin structure. The known methyl-DNA-binding proteins have unique domains responsible for DNA methylation recognition: (1) the methyl-CpG-binding domain (MBD), (2) the SET- and RING finger-associated domain (SRA), and (3) some of TF families, such as the C2H2 zinc finger domain, basic helix-loop-helix (bHLH), basic leucine-zipper (bZIP), and homeodomain proteins. Structural analyses have revealed that each domain has a characteristic methylated DNA-binding pattern, and the difference in the recognition mechanisms renders the DNA methylation mark able to transmit complicated biological information. Recent genetic and genomic studies have revealed novel functions of methyl-DNA-binding proteins. These emerging data have also provided glimpses into how methyl-DNA-binding proteins possess unique features and, presumably, functions. In this chapter, we summarize structural and biochemical analyses elucidating the mechanisms for recognition of DNA methylation and correlate this information with emerging genomic and functional data.
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Abbreviations
- 5caC:
-
5-carboxylcytosine
- 5fC:
-
5-formylcytosine
- 5hmC:
-
5-hydroxymethylcytosine
- 5mC:
-
5-methylcytosine
- bHLH:
-
Basic helix-loop-helix
- bZIP:
-
Basic leucine-zipper
- CTCF:
-
Multidomain CCCTC-binding factor
- DNMT:
-
DNA methyltransferase
- GD:
-
Glycosylase domain
- MARs/SARs:
-
Matrix/scaffold attachment regions
- MBD:
-
Methyl-CpG-binding domain
- NSC:
-
Neural stem cell
- NuRD:
-
Nucleosome remodeling deacetylase
- PHD:
-
Plant homeodomain
- RING:
-
Really interesting new gene domain
- SRA:
-
SET- and RING finger-associated domain
- TF:
-
Transcriptional factor
- TRD:
-
Transcriptional repression domain
- TTD:
-
Tandem Tudor domain
- UBL:
-
Ubiquitin-like domain
- ZF:
-
Zinc finger
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Acknowledgments
This work was supported by funds from the National Natural Science Foundation of China (Number 31770834 to K.L) and the funds from Central China Normal University (Number 31101200001 to J.M. and CCNU19TS084 to K.L). This work was also supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, NIH (ES101965 to P.A.W.). Due to the limited space, we apologize to those whose original work could not be cited in this chapter.
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Liu, K., Shimbo, T., Song, X., Wade, P.A., Min, J. (2022). Proteins That Read DNA Methylation. In: Jeltsch, A., Jurkowska, R.Z. (eds) DNA Methyltransferases - Role and Function. Advances in Experimental Medicine and Biology, vol 1389. Springer, Cham. https://doi.org/10.1007/978-3-031-11454-0_11
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