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http://dx.doi.org/10.18419/opus-13700
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DC Element | Wert | Sprache |
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dc.contributor.author | Choudalakis, Michel | - |
dc.contributor.author | Kungulovski, Goran | - |
dc.contributor.author | Mauser, Rebekka | - |
dc.contributor.author | Bashtrykov, Pavel | - |
dc.contributor.author | Jeltsch, Albert | - |
dc.date.accessioned | 2023-11-06T13:34:01Z | - |
dc.date.available | 2023-11-06T13:34:01Z | - |
dc.date.issued | 2023 | de |
dc.identifier.issn | 0961-8368 | - |
dc.identifier.issn | 1469-896X | - |
dc.identifier.other | 1870493133 | - |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-137192 | de |
dc.identifier.uri | http://elib.uni-stuttgart.de/handle/11682/13719 | - |
dc.identifier.uri | http://dx.doi.org/10.18419/opus-13700 | - |
dc.description.abstract | UHRF1 is an essential chromatin protein required for DNA methylation maintenance, mammalian development, and gene regulation. We investigated the Tandem-Tudor domain (TTD) of human UHRF1 that is known to bind H3K9me2/3 histones and is a major driver of UHRF1 localization in cells. We verified binding to H3K9me2/3 but unexpectedly discovered stronger binding to H3 peptides and mononucleosomes containing K9me2/3 with additional K4me1. We investigated the combined binding of TTD to H3K4me1-K9me2/3 versus H3K9me2/3 alone, engineered mutants with specific and differential changes of binding, and discovered a novel read-out mechanism for H3K4me1 in an H3K9me2/3 context that is based on the interaction of R207 with the H3K4me1 methyl group and on counting the H-bond capacity of H3K4. Individual TTD mutants showed up to a 10,000-fold preference for the double-modified peptides, suggesting that after a conformational change, WT TTD could exhibit similar effects. The frequent appearance of H3K4me1-K9me2 regions in human chromatin demonstrated in our TTD chromatin pull-down and ChIP-western blot data suggests that it has specific biological roles. Chromatin pull-down of TTD from HepG2 cells and full-length murine UHRF1 ChIP-seq data correlate with H3K4me1 profiles indicating that the H3K4me1-K9me2/3 interaction of TTD influences chromatin binding of full-length UHRF1. We demonstrate the H3K4me1-K9me2/3 specific binding of UHRF1-TTD to enhancers and promoters of cell-type-specific genes at the flanks of cell-type-specific transcription factor binding sites, and provided evidence supporting an H3K4me1-K9me2/3 dependent and TTD mediated downregulation of these genes by UHRF1. All these findings illustrate the important physiological function of UHRF1-TTD binding to H3K4me1-K9me2/3 double marks in a cellular context. | en |
dc.description.sponsorship | Universität Stuttgart | de |
dc.description.sponsorship | Projekt DEAL | de |
dc.language.iso | en | de |
dc.relation.uri | doi:10.1002/pro.4760 | de |
dc.rights | info:eu-repo/semantics/openAccess | de |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | de |
dc.subject.ddc | 540 | de |
dc.title | Refined read‐out : the hUHRF1 Tandem‐Tudor domain prefers binding to histone H3 tails containing K4me1 in the context of H3K9me2/3 | en |
dc.type | article | de |
dc.date.updated | 2023-10-10T16:42:48Z | - |
ubs.fakultaet | Chemie | de |
ubs.institut | Institut für Biochemie und Technische Biochemie | de |
ubs.publikation.seiten | 25 | de |
ubs.publikation.source | Protein science 32 (2023), No. e4760 | de |
ubs.publikation.typ | Zeitschriftenartikel | de |
Enthalten in den Sammlungen: | 03 Fakultät Chemie |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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PRO_PRO4760.pdf | 6,91 MB | Adobe PDF | Öffnen/Anzeigen |
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