Automethylation of PRC2 promotes H3K27 methylation and is impaired in H3K27M pediatric glioma.
H3K27M
PRC2
Polycomb
automethylation
pediatric glioma
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
14
05
2019
accepted:
12
08
2019
pubmed:
7
9
2019
medline:
20
11
2019
entrez:
7
9
2019
Statut:
ppublish
Résumé
The histone methyltransferase activity of PRC2 is central to the formation of H3K27me3-decorated facultative heterochromatin and gene silencing. In addition, PRC2 has been shown to automethylate its core subunits, EZH1/EZH2 and SUZ12. Here, we identify the lysine residues at which EZH1/EZH2 are automethylated with EZH2-K510 and EZH2-K514 being the major such sites in vivo. Automethylated EZH2/PRC2 exhibits a higher level of histone methyltransferase activity and is required for attaining proper cellular levels of H3K27me3. While occurring independently of PRC2 recruitment to chromatin, automethylation promotes PRC2 accessibility to the histone H3 tail. Intriguingly, EZH2 automethylation is significantly reduced in diffuse intrinsic pontine glioma (DIPG) cells that carry a lysine-to-methionine substitution in histone H3 (H3K27M), but not in cells that carry either EZH2 or EED mutants that abrogate PRC2 allosteric activation, indicating that H3K27M impairs the intrinsic activity of PRC2. Our study demonstrates a PRC2 self-regulatory mechanism through its EZH1/2-mediated automethylation activity.
Identifiants
pubmed: 31488577
pii: gad.328773.119
doi: 10.1101/gad.328773.119
pmc: PMC6771381
doi:
Substances chimiques
Histones
0
Protein Subunits
0
Polycomb Repressive Complex 2
EC 2.1.1.43
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1428-1440Subventions
Organisme : NCI NIH HHS
ID : R01 CA199652
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAAA NIH HHS
ID : K99 AA024837
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM110174
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009140
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA196539
Pays : United States
Informations de copyright
© 2019 Lee et al.; Published by Cold Spring Harbor Laboratory Press.
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