Publikation:

Evolved DNA Duplex Readers for Strand-Asymmetrically Modified 5-Hydroxymethylcytosine/5-Methylcytosine CpG Dyads

Lade...
Vorschaubild

Dateien

Buchmuller_2-1c7uuyf11svkl9.pdf
Buchmuller_2-1c7uuyf11svkl9.pdfGröße: 3.04 MBDownloads: 237

Datum

2022

Autor:innen

Buchmuller, Benjamin C.
Singh, Himanshu
Palei, Shubhendu
Linser, Rasmus

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

ArXiv-ID

Internationale Patentnummer

Link zur Lizenz

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Open Access Hybrid
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Journal of the American Chemical Society. American Chemical Society (ACS). 2022, 144(7), pp. 2987-2993. ISSN 0002-7863. eISSN 1520-5126. Available under: doi: 10.1021/jacs.1c10678

Zusammenfassung

5-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.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
540 Chemie

Schlagwörter

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690BUCHMULLER, Benjamin C., Jessica DRÖDEN, Himanshu SINGH, Shubhendu PALEI, Malte DRESCHER, Rasmus LINSER, Daniel SUMMERER, 2022. Evolved DNA Duplex Readers for Strand-Asymmetrically Modified 5-Hydroxymethylcytosine/5-Methylcytosine CpG Dyads. In: Journal of the American Chemical Society. American Chemical Society (ACS). 2022, 144(7), pp. 2987-2993. ISSN 0002-7863. eISSN 1520-5126. Available under: doi: 10.1021/jacs.1c10678
BibTex
@article{Buchmuller2022Evolv-57259,
  year={2022},
  doi={10.1021/jacs.1c10678},
  title={Evolved DNA Duplex Readers for Strand-Asymmetrically Modified 5-Hydroxymethylcytosine/5-Methylcytosine CpG Dyads},
  number={7},
  volume={144},
  issn={0002-7863},
  journal={Journal of the American Chemical Society},
  pages={2987--2993},
  author={Buchmuller, Benjamin C. and Dröden, Jessica and Singh, Himanshu and Palei, Shubhendu and Drescher, Malte and Linser, Rasmus and Summerer, Daniel}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/57259">
    <dc:creator>Dröden, Jessica</dc:creator>
    <dc:creator>Linser, Rasmus</dc:creator>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57259/1/Buchmuller_2-1c7uuyf11svkl9.pdf"/>
    <dc:creator>Singh, Himanshu</dc:creator>
    <dcterms:abstract xml:lang="eng">5-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.</dcterms:abstract>
    <dcterms:title>Evolved DNA Duplex Readers for Strand-Asymmetrically Modified 5-Hydroxymethylcytosine/5-Methylcytosine CpG Dyads</dcterms:title>
    <dc:contributor>Buchmuller, Benjamin C.</dc:contributor>
    <dc:contributor>Linser, Rasmus</dc:contributor>
    <dc:contributor>Palei, Shubhendu</dc:contributor>
    <dc:creator>Summerer, Daniel</dc:creator>
    <dc:contributor>Summerer, Daniel</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-04-11T14:55:32Z</dcterms:available>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/57259"/>
    <dc:contributor>Singh, Himanshu</dc:contributor>
    <dc:contributor>Dröden, Jessica</dc:contributor>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Drescher, Malte</dc:creator>
    <dc:creator>Palei, Shubhendu</dc:creator>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57259/1/Buchmuller_2-1c7uuyf11svkl9.pdf"/>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-04-11T14:55:32Z</dc:date>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:language>eng</dc:language>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:creator>Buchmuller, Benjamin C.</dc:creator>
    <dc:contributor>Drescher, Malte</dc:contributor>
    <dcterms:issued>2022</dcterms:issued>
  </rdf:Description>
</rdf:RDF>

Interner Vermerk

xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter

Kontakt
URL der Originalveröffentl.

Prüfdatum der URL

Prüfungsdatum der Dissertation

Finanzierungsart

Kommentar zur Publikation

Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Diese Publikation teilen