Faculty, Staff and Student Publications
Publication Date
4-1-2024
Journal
Journal of Molecular Biology
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.
Keywords
Acetylation, Chromatin, Histones, Nucleosomes, Lysine Acetyltransferase 5, Tudor Domain, Humans
DOI
10.1016/j.jmb.2023.168414
PMID
38141874
PMCID
PMC10957329
PubMedCentral® Posted Date
4-1-2025
PubMedCentral® Full Text Version
Author MSS
Graphical Abstract
Published Open-Access
yes
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