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dc.contributor.author
Szczesnik, Tomasz
dc.contributor.author
Chu, Lendy
dc.contributor.author
Ho, Joshua W.K
dc.contributor.author
Sherwood, Richard I.
dc.date.accessioned
2020-10-13T09:40:41Z
dc.date.available
2020-09-28T02:46:45Z
dc.date.available
2020-09-29T15:07:02Z
dc.date.available
2020-10-13T09:40:41Z
dc.date.issued
2020-09-23
dc.identifier.issn
2405-4720
dc.identifier.other
10.1016/j.cels.2020.08.004
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/442918
dc.identifier.doi
10.3929/ethz-b-000442918
dc.description.abstract
Predicting where transcription factors bind in the genome from their in vitro DNA-binding affinity is confounded by the large number of possible interactions with nearby transcription factors. To characterize the in vivo binding logic for the Wnt effector Tcf7l2, we developed a high-throughput screening platform in which thousands of synthesized DNA phrases are inserted into a specific genomic locus, followed by measurement of Tcf7l2 binding by DamID. Using this platform at two genomic loci in mouse embryonic stem cells, we show that while the binding of Tcf7l2 closely follows the in vitro motif-binding strength and is influenced by local chromatin accessibility, it is also strongly affected by the surrounding 99 bp of sequence. Through controlled sequence perturbation, we show that Oct4 and Klf4 motifs promote Tcf7l2 binding, particularly in the adjacent ∼50 bp and oscillating with a 10.8-bp phasing relative to these cofactor motifs, which matches the turn of a DNA helix. © 2020 The Authors Transcription factor binding in cells depends on interactions with other proteins. We have developed a high-throughput screening platform to study transcription factor binding strength at thousands of variable sequences in a fixed genomic locus. We find that binding of the Wnt effector Tcf7l2 in mouse embryonic stem cells depends on proximity and phasing that matches the turn of the DNA helix relative to its cofactors Oct4 and Klf4. © 2020 The Authors
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title
A High-Throughput Genome-Integrated Assay Reveals Spatial Dependencies Governing Tcf7l2 Binding
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
ethz.journal.title
Cell Systems
ethz.journal.volume
11
en_US
ethz.journal.issue
3
en_US
ethz.journal.abbreviated
Cell Syst
ethz.pages.start
315
en_US
ethz.pages.end
327
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Amsterdam
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2020-09-28T02:46:49Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-09-29T15:07:13Z
ethz.rosetta.lastUpdated
2021-02-15T18:04:48Z
ethz.rosetta.versionExported
true
ethz.COinS
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