{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xuan F"],"funding":["CPRIT","National Cancer Institute","NCI NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["168414"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10957329"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["436(7)"],"pubmed_abstract":["The lysine acetyltransferase KAT5 is a pivotal enzyme responsible for catalyzing histone H4 acetylation in cells. In addition to its indispensable HAT domain, KAT5 also encompasses a conserved Tudor-knot domain at its N-terminus. However, the function of this domain remains elusive, with conflicting findings regarding its role as a histone reader. In our study, we have employed a CRISPR tiling array approach and unveiled the Tudor-knot motif as an essential domain for cell survival. The Tudor-knot domain does not bind to histone tails and is not required for KAT5's chromatin occupancy. However, its absence leads to a global reduction in histone acetylation, accompanied with genome-wide alterations in gene expression that consequently result in diminished cell viability. Mechanistically, we find that the Tudor-knot domain regulates KAT5's HAT activity on nucleosomes by fine-tuning substrate accessibility. In summary, our study uncovers the Tudor-knot motif as an essential domain for cell survival and reveals its critical role in modulating KAT5's catalytic efficiency on nucleosome and KAT5-dependent transcriptional programs critical for cell viability."],"journal":["Journal of molecular biology"],"pubmed_title":["The Tudor-knot Domain of KAT5 Regulates Nucleosomal Substrate Acetylation."],"pmcid":["PMC10957329"],"funding_grant_id":["CA268440","R01 CA204020","CA204020","GM137927","R35 GM137927","R01 CA268440","R01 CA255506","CA260666","CA255506","R01 CA260666","RR160097"],"pubmed_authors":["Wen H","He W","Xuan F","Huang M","Xuan H","Xu H","Shi X"],"additional_accession":[]},"is_claimable":false,"name":"The Tudor-knot Domain of KAT5 Regulates Nucleosomal Substrate Acetylation.","description":"The lysine acetyltransferase KAT5 is a pivotal enzyme responsible for catalyzing histone H4 acetylation in cells. In addition to its indispensable HAT domain, KAT5 also encompasses a conserved Tudor-knot domain at its N-terminus. However, the function of this domain remains elusive, with conflicting findings regarding its role as a histone reader. In our study, we have employed a CRISPR tiling array approach and unveiled the Tudor-knot motif as an essential domain for cell survival. The Tudor-knot domain does not bind to histone tails and is not required for KAT5's chromatin occupancy. However, its absence leads to a global reduction in histone acetylation, accompanied with genome-wide alterations in gene expression that consequently result in diminished cell viability. Mechanistically, we find that the Tudor-knot domain regulates KAT5's HAT activity on nucleosomes by fine-tuning substrate accessibility. In summary, our study uncovers the Tudor-knot motif as an essential domain for cell survival and reveals its critical role in modulating KAT5's catalytic efficiency on nucleosome and KAT5-dependent transcriptional programs critical for cell viability.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-27T03:21:54.843Z","creation":"2025-07-04T03:05:53.344Z"},"accession":"S-EPMC10957329","cross_references":{"pubmed":["38141874"],"doi":["10.1016/j.jmb.2023.168414"]}}