Evolved DNA duplex readers for strand-asymmetrically modified 5-hydroxymethylcytosine/5-methylcytosine CpG dyads

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dc.contributor.authorBuchmuller, Benjamin C.
dc.contributor.authorDröden, Jessica
dc.contributor.authorSingh, Himanshu
dc.contributor.authorPalei, Shubhendu
dc.contributor.authorDrescher , Malte
dc.contributor.authorLinser, Rasmus
dc.contributor.authorSummerer, Daniel
dc.date.accessioned2026-01-15T07:50:12Z
dc.date.available2026-01-15T07:50:12Z
dc.date.issued2022-02-14
dc.description.abstract5-Methylcytosine (mC) and 5-hydroxymethylcytosine (hmC), the two main epigenetic modifications of mammalian DNA, exist in symmetric and asymmetric combinations in the two strands of CpG dyads. However, revealing such combinations in single DNA duplexes is a significant challenge. Here, we evolve methyl-CpG-binding domains (MBDs) derived from MeCP2 by bacterial cell surface display, resulting in the first affinity probes for hmC/mC CpGs. One mutant has low nanomolar affinity for a single hmC/mC CpG, discriminates against all 14 other modified CpG dyads, and rivals the selectivity of wild-type MeCP2. Structural studies indicate that this protein has a conserved scaffold and recognizes hmC and mC with two dedicated sets of residues. The mutant allows us to selectively address and enrich hmC/mC-containing DNA fragments from genomic DNA backgrounds. We anticipate that this novel probe will be a versatile tool to unravel the function of hmC/mC marks in diverse aspects of chromatin biology.en
dc.identifier.urihttp://hdl.handle.net/2003/44668
dc.language.isoen
dc.relation.ispartofseriesJournal of the American Chemical Society; 144(7)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddc540
dc.subject.rswkChromatin
dc.subject.rswkEpigenetik
dc.subject.rswkDNS-Bindungsproteine
dc.subject.rswkDNS-Methyltransferase
dc.titleEvolved DNA duplex readers for strand-asymmetrically modified 5-hydroxymethylcytosine/5-methylcytosine CpG dyadsen
dc.typeText
dc.type.publicationtypeArticle
dcterms.accessRightsopen access
eldorado.dnb.deposittrue
eldorado.doi.registerfalse
eldorado.secondarypublicationtrue
eldorado.secondarypublication.primarycitationBuchmuller, B., Dröden, J., Singh, H., Palei, S., Drescher, M., Linser, R., & Summerer, D. (2022). Evolved DNA duplex readers for strand-asymmetrically modified 5-hydroxymethylcytosine/5-methylcytosine CpG dyads. Journal of the American Chemical Society, 144(7), 2987–2993. https://doi.org/10.1021/jacs.1c10678
eldorado.secondarypublication.primaryidentifierhttps://doi.org/10.1021/jacs.1c10678

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Fakultät fĂ¼r Chemie und Chemische Biologie