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• W4385422346 abstract "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 vs . H3K9me2/3, 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 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 demonstrated in our TTD pulldown and ChIP-western blot data suggests that it has specific biological roles. Chromatin pull-down of TTD from HepG2 cells and ChIP-seq data of full-length murine UHRF1 correlate with H3K4me1 profiles indicating that the H3K4me1-K9me2/3 interaction of TTD influences chromatin binding of full-length UHRF1. We demonstrated 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 down-regulation of these genes by UHRF1, illustrating the physiological function of UHRF1-TTD binding to H3K4me1-K9me2/3 double marks in a cellular context." @default.
• W4385422346 created "2023-08-01" @default.
• W4385422346 creator A5004194558 @default.
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• W4385422346 creator A5029326513 @default.
• W4385422346 creator A5070638287 @default.
• W4385422346 creator A5079254200 @default.
• W4385422346 date "2023-07-30" @default.
• W4385422346 modified "2023-09-27" @default.
• W4385422346 title "Refined read-out: The hUHRF1 Tandem-Tudor domain prefers binding to histone H3 tails containing K4me1 in the context of H3K9me2/3" @default.
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• W4385422346 doi "https://doi.org/10.1101/2023.07.30.551139" @default.
• W4385422346 hasPublicationYear "2023" @default.
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