EZH2 oncogenic mutations drive epigenetic, transcriptional, and structural changes within chromatin domains.
Animals
Cell Line, Tumor
Chromatin
/ genetics
DNA Methylation
/ genetics
Enhancer of Zeste Homolog 2 Protein
/ genetics
Epigenesis, Genetic
/ genetics
Epigenomics
/ methods
Gene Expression Regulation, Neoplastic
/ genetics
Gene Silencing
/ physiology
Histones
/ genetics
Humans
Mice
Mutation
/ genetics
Promoter Regions, Genetic
/ genetics
Transcription, Genetic
/ genetics
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
27
04
2018
accepted:
17
12
2018
pubmed:
30
1
2019
medline:
25
4
2019
entrez:
30
1
2019
Statut:
ppublish
Résumé
Chromatin is organized into topologically associating domains (TADs) enriched in distinct histone marks. In cancer, gain-of-function mutations in the gene encoding the enhancer of zeste homolog 2 protein (EZH2) lead to a genome-wide increase in histone-3 Lys27 trimethylation (H3K27me3) associated with transcriptional repression. However, the effects of these epigenetic changes on the structure and function of chromatin domains have not been explored. Here, we found a functional interplay between TADs and epigenetic and transcriptional changes mediated by mutated EZH2. Altered EZH2 (p.Tyr646* (EZH2
Identifiants
pubmed: 30692681
doi: 10.1038/s41588-018-0338-y
pii: 10.1038/s41588-018-0338-y
doi:
Substances chimiques
Chromatin
0
Histones
0
EZH2 protein, human
EC 2.1.1.43
Enhancer of Zeste Homolog 2 Protein
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
517-528Références
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