| First Author | Luo C | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 30644360 | Mgi Jnum | J:278750 |
| Mgi Id | MGI:6358925 | Doi | 10.7554/eLife.40197 |
| Citation | Luo C, et al. (2019) Global DNA methylation remodeling during direct reprogramming of fibroblasts to neurons. Elife 8:e40197 |
| abstractText | Direct reprogramming of fibroblasts to neurons induces widespread cellular and transcriptional reconfiguration. Here, we characterized global epigenomic changes during the direct reprogramming of mouse fibroblasts to neurons using whole-genome base-resolution DNA methylation (mC) sequencing. We found that the pioneer transcription factor Ascl1 alone is sufficient for inducing the uniquely neuronal feature of non-CG methylation (mCH), but co-expression of Brn2 and Mytl1 was required to establish a global mCH pattern reminiscent of mature cortical neurons. Ascl1 alone induced promoter CG methylation (mCG) of fibroblast specific genes, while BAM overexpression additionally targets a competing myogenic program and directs a more faithful conversion to neuronal cells. Ascl1 induces local demethylation at its binding sites. Surprisingly, co-expression with Brn2 and Mytl1 inhibited the ability of Ascl1 to induce demethylation, suggesting a contextual regulation of transcription factor - epigenome interaction. Finally, we found that de novo methylation by DNMT3A is required for efficient neuronal reprogramming. |
