Young LINE-1 transposon 5' UTRs marked by elongation factor ELL3 function as enhancers to regulate naïve pluripotency in embryonic stem cells.
Nat Cell Biol
; 25(9): 1319-1331, 2023 09.
Article
de En
| MEDLINE
| ID: mdl-37591949
ABSTRACT
LINE-1s are the major clade of retrotransposons with autonomous retrotransposition activity. Despite the potential genotoxicity, LINE-1s are highly activated in early embryos. Here we show that a subset of young LINE-1s, L1Md_Ts, are marked by the RNA polymerase II elongation factor ELL3, and function as enhancers in mouse embryonic stem cells. ELL3 depletion dislodges the DNA hydroxymethylase TET1 and the co-repressor SIN3A from L1Md_Ts, but increases the enrichment of the Bromodomain protein BRD4, leading to loss of 5hmC, gain of H3K27ac, and upregulation of the L1Md_T nearby genes. Specifically, ELL3 occupies and represses the L1Md_T-based enhancer located within Akt3, which encodes a key regulator of AKT pathway. ELL3 is required for proper ERK activation and efficient shutdown of naïve pluripotency through inhibiting Akt3 during naïve-primed transition. Our study reveals that the enhancer function of a subset of young LINE-1s controlled by ELL3 in transcription regulation and mouse early embryo development.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Facteurs de transcription
/
Protéines nucléaires
Limites:
Animals
Langue:
En
Journal:
Nat Cell Biol
Année:
2023
Type de document:
Article
Pays d'affiliation:
Chine