| First Author | Ikeda T | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 1387 |
| PubMed ID | 29643333 | Mgi Jnum | J:265721 |
| Mgi Id | MGI:6158051 | Doi | 10.1038/s41467-018-03748-1 |
| Citation | Ikeda T, et al. (2018) Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs. Nat Commun 9(1):1387 |
| abstractText | Multicellular organisms consist of multiple cell types. The identity of these cells is primarily maintained by cell-type-specific gene expression programs; however, mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease beta-actin monomer quantity result in the nuclear accumulation of Mkl1 and the activation of Srf, which downregulate cell-type-specific genes and alter the epigenetics of regulatory regions and chromatin organization. Mice overexpressing Srf exhibit various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases. |
