| First Author | Meng S | Year | 2023 |
| Journal | Nat Cell Biol | Volume | 25 |
| Issue | 9 | Pages | 1319-1331 |
| PubMed ID | 37591949 | Mgi Jnum | J:361580 |
| Mgi Id | MGI:7859242 | Doi | 10.1038/s41556-023-01211-y |
| Citation | Meng S, et al. (2023) Young LINE-1 transposon 5' UTRs marked by elongation factor ELL3 function as enhancers to regulate naive pluripotency in embryonic stem cells. Nat Cell Biol 25(9):1319-1331 |
| abstractText | 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 naive pluripotency through inhibiting Akt3 during naive-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. |
