Summary information and primary citation
- PDB-id
-
8hah;
DSSR-derived features in text and
JSON formats
- Class
- transferase-DNA
- Method
- cryo-EM (3.9 Å)
- Summary
- cryo-EM structure of the p300 catalytic core bound to
the h4k12ack16ac nucleosome, class 2 (3.9 angstrom
resolution)
- Reference
-
Kikuchi M, Morita S, Wakamori M, Sato S, Uchikubo-Kamo T,
Suzuki T, Dohmae N, Shirouzu M, Umehara T (2023):
"Epigenetic
mechanisms to propagate histone acetylation by
p300/CBP." Nat Commun, 14,
4103. doi: 10.1038/s41467-023-39735-4.
- Abstract
- Histone acetylation is important for the activation of
gene transcription but little is known about its direct
read/write mechanisms. Here, we report cryogenic electron
microscopy structures in which a p300/CREB-binding protein
(CBP) multidomain monomer recognizes histone H4 N-terminal
tail (NT) acetylation (ac) in a nucleosome and acetylates
non-H4 histone NTs within the same nucleosome. p300/CBP not
only recognized H4NTac via the bromodomain pocket
responsible for reading, but also interacted with the DNA
minor grooves via the outside of that pocket. This directed
the catalytic center of p300/CBP to one of the non-H4
histone NTs. The primary target that p300 writes by reading
H4NTac was H2BNT, and H2BNTac promoted H2A-H2B dissociation
from the nucleosome. We propose a model in which p300/CBP
replicates histone N-terminal tail acetylation within the
H3-H4 tetramer to inherit epigenetic storage, and
transcribes it from the H3-H4 tetramer to the H2B-H2A
dimers to activate context-dependent gene transcription
through local nucleosome destabilization.
