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Characterization of How DNA Modifications Affect DNA Binding by C2H2 Zinc Finger Proteins

Overview
Journal Methods Enzymol
Specialty Biochemistry
Date 2016 Jul 4
PMID 27372763
Citations 23
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Abstract

Much is known about vertebrate DNA methylation and oxidation; however, much less is known about how modified cytosine residues within particular sequences are recognized. Among the known methylated DNA-binding domains, the Cys2-His2 zinc finger (ZnF) protein superfamily is the largest with hundreds of members, each containing tandem ZnFs ranging from 3 to >30 fingers. We have begun to biochemically and structurally characterize these ZnFs not only on their sequence specificity but also on their sensitivity to various DNA modifications. Rather than following published methods of refolding insoluble ZnF arrays, we have expressed and purified soluble forms of ZnFs, ranging in size from a tandem array of two to six ZnFs, from seven different proteins. We also describe a fluorescence polarization assay to measure ZnFs affinity with oligonucleotides containing various modifications and our approaches for cocrystallization of ZnFs with oligonucleotides.

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References
1.
Liu Y, Toh H, Sasaki H, Zhang X, Cheng X . An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence. Genes Dev. 2012; 26(21):2374-9. PMC: 3489995. DOI: 10.1101/gad.202200.112. View

2.
Guy J, Cheval H, Selfridge J, Bird A . The role of MeCP2 in the brain. Annu Rev Cell Dev Biol. 2011; 27:631-52. DOI: 10.1146/annurev-cellbio-092910-154121. View

3.
Hashimoto H, Horton J, Zhang X, Cheng X . UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications. Epigenetics. 2008; 4(1):8-14. PMC: 2661099. DOI: 10.4161/epi.4.1.7370. View

4.
Jenuwein T, Laible G, Dorn R, Reuter G . SET domain proteins modulate chromatin domains in eu- and heterochromatin. Cell Mol Life Sci. 1998; 54(1):80-93. PMC: 11147257. DOI: 10.1007/s000180050127. View

5.
Ramsahoye B, Biniszkiewicz D, Lyko F, Clark V, Bird A, Jaenisch R . Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci U S A. 2000; 97(10):5237-42. PMC: 25812. DOI: 10.1073/pnas.97.10.5237. View