PRAMEL7 and CUL2 decrease NuRD stability to establish ground-state pluripotency.
EMBO Rep
; 25(3): 1453-1468, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38332149
ABSTRACT
Pluripotency is established in E4.5 preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of pluripotency, however, their gene expression signature only partially resembles that of developmental ground-state. Induced PRAMEL7 expression, a protein highly expressed in the ICM but lowly expressed in ESCs, reprograms developmentally advanced ESC+serum into ground-state pluripotency by inducing a gene expression signature close to developmental ground-state. However, how PRAMEL7 reprograms gene expression remains elusive. Here we show that PRAMEL7 associates with Cullin2 (CUL2) and this interaction is required to establish ground-state gene expression. PRAMEL7 recruits CUL2 to chromatin and targets regulators of repressive chromatin, including the NuRD complex, for proteasomal degradation. PRAMEL7 antagonizes NuRD-mediated repression of genes implicated in pluripotency by decreasing NuRD stability and promoter association in a CUL2-dependent manner. Our data link proteasome degradation pathways to ground-state gene expression, offering insights to generate in vitro models to reproduce the in vivo ground-state pluripotency.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pluripotent Stem Cells
Language:
En
Journal:
EMBO Rep
Year:
2024
Document type:
Article