The Tudor-knot Domain of KAT5 Regulates Nucleosomal Substrate Acetylation.
J Mol Biol
; 436(7): 168414, 2024 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-38141874
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histones
/
Nucleosomes
/
Tudor Domain
/
Lysine Acetyltransferase 5
Limits:
Humans
Language:
En
Journal:
J Mol Biol
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
Netherlands