| First Author | Kadhim AZ | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 8711 |
| PubMed ID | 39379383 | Mgi Jnum | J:355262 |
| Mgi Id | MGI:7737975 | Doi | 10.1038/s41467-024-52801-9 |
| Citation | Kadhim AZ, et al. (2024) Transcriptional coactivator MED15 is required for beta cell maturation. Nat Commun 15(1):8711 |
| abstractText | Mediator, a co-regulator complex required for RNA Polymerase II activity, interacts with tissue-specific transcription factors to regulate development and maintain homeostasis. We observe reduced Mediator subunit MED15 expression in endocrine hormone-producing pancreatic islets isolated from people living with type 2 diabetes and sought to understand how MED15 and Mediator control gene expression programs important for the function of insulin-producing beta-cells. Here we show that Med15 is expressed during mouse beta-cell development and maturation. Knockout of Med15 in mouse beta-cells causes defects in beta-cell maturation without affecting beta-cell mass or insulin expression. ChIP-seq and co-immunoprecipitation analyses found that Med15 binds beta-cell transcription factors Nkx6-1 and NeuroD1 to regulate key beta-cell maturation genes. In support of a conserved role during human development, human embryonic stem cell-derived beta-like cells, genetically engineered to express high levels of MED15, express increased levels of maturation markers. We provide evidence of a conserved role for Mediator in beta-cell maturation and demonstrate an additional layer of control that tunes beta-cell transcription factor function. |
