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- Publisher Website: 10.1016/j.cels.2020.08.004
- Scopus: eid_2-s2.0-85091303214
- PMID: 32910904
- WOS: WOS:000574601700010
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Article: A High-Throughput Genome-Integrated Assay Reveals Spatial Dependencies Governing Tcf7l2 Binding
Title | A High-Throughput Genome-Integrated Assay Reveals Spatial Dependencies Governing Tcf7l2 Binding |
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Authors | |
Keywords | Tcf7l2 DamID transcription factor CRISPR-Cas9 Gaussian process |
Issue Date | 2020 |
Publisher | Cell Press. The Journal's web site is located at http://www.cell.com/cell-systems/home |
Citation | Cell Systems, 2020, v. 11 n. 3, p. 315-327.E5 How to Cite? |
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. |
Persistent Identifier | http://hdl.handle.net/10722/287128 |
ISSN | 2023 Impact Factor: 9.0 2023 SCImago Journal Rankings: 4.872 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Szczesnik, T | - |
dc.contributor.author | Chu, L | - |
dc.contributor.author | Ho, JWK | - |
dc.contributor.author | Sherwood, RI | - |
dc.date.accessioned | 2020-09-22T02:56:11Z | - |
dc.date.available | 2020-09-22T02:56:11Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Cell Systems, 2020, v. 11 n. 3, p. 315-327.E5 | - |
dc.identifier.issn | 2405-4712 | - |
dc.identifier.uri | http://hdl.handle.net/10722/287128 | - |
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. | - |
dc.language | eng | - |
dc.publisher | Cell Press. The Journal's web site is located at http://www.cell.com/cell-systems/home | - |
dc.relation.ispartof | Cell Systems | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Tcf7l2 | - |
dc.subject | DamID | - |
dc.subject | transcription factor | - |
dc.subject | CRISPR-Cas9 | - |
dc.subject | Gaussian process | - |
dc.title | A High-Throughput Genome-Integrated Assay Reveals Spatial Dependencies Governing Tcf7l2 Binding | - |
dc.type | Article | - |
dc.identifier.email | Ho, JWK: jwkho@hku.hk | - |
dc.identifier.authority | Ho, JWK=rp02436 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.cels.2020.08.004 | - |
dc.identifier.pmid | 32910904 | - |
dc.identifier.pmcid | PMC7530048 | - |
dc.identifier.scopus | eid_2-s2.0-85091303214 | - |
dc.identifier.hkuros | 314430 | - |
dc.identifier.volume | 11 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 315 | - |
dc.identifier.epage | 327.E5 | - |
dc.identifier.isi | WOS:000574601700010 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 2405-4712 | - |