EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells.
Adult
Animals
Cell Line, Tumor
Chromatin
/ metabolism
Female
HEK293 Cells
Histones
/ metabolism
Humans
Male
Mice
Mice, Knockout
Mutation
Oncogene Proteins
/ genetics
Oogenesis
Ovary
/ cytology
Ovum
/ metabolism
Polycomb Repressive Complex 2
/ metabolism
Recombinant Proteins
/ genetics
Sf9 Cells
Spermatogenesis
Spermatozoa
/ metabolism
Testis
/ cytology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 08 2019
26 08 2019
Historique:
received:
05
11
2018
accepted:
06
08
2019
entrez:
28
8
2019
pubmed:
28
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
The Polycomb group of proteins is required for the proper orchestration of gene expression due to its role in maintaining transcriptional silencing. It is composed of several chromatin modifying complexes, including Polycomb Repressive Complex 2 (PRC2), which deposits H3K27me2/3. Here, we report the identification of a cofactor of PRC2, EZHIP (EZH1/2 Inhibitory Protein), expressed predominantly in the gonads. EZHIP limits the enzymatic activity of PRC2 and lessens the interaction between the core complex and its accessory subunits, but does not interfere with PRC2 recruitment to chromatin. Deletion of Ezhip in mice leads to a global increase in H3K27me2/3 deposition both during spermatogenesis and at late stages of oocyte maturation. This does not affect the initial number of follicles but is associated with a reduction of follicles in aging. Our results suggest that mature oocytes Ezhip-/- might not be fully functional and indicate that fertility is strongly impaired in Ezhip-/- females. Altogether, our study uncovers EZHIP as a regulator of chromatin landscape in gametes.
Identifiants
pubmed: 31451685
doi: 10.1038/s41467-019-11800-x
pii: 10.1038/s41467-019-11800-x
pmc: PMC6710278
doi:
Substances chimiques
AU022751 protein, mouse
0
Chromatin
0
EZHIP protein, human
0
Histones
0
Oncogene Proteins
0
Recombinant Proteins
0
Polycomb Repressive Complex 2
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
3858Commentaires et corrections
Type : CommentIn
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