| First Author | Yu Y | Year | 2013 |
| Journal | Cell | Volume | 152 |
| Issue | 1-2 | Pages | 248-61 |
| PubMed ID | 23332759 | Mgi Jnum | J:193501 |
| Mgi Id | MGI:5468625 | Doi | 10.1016/j.cell.2012.12.006 |
| Citation | Yu Y, et al. (2013) Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation. Cell 152(1-2):248-61 |
| abstractText | Establishment of oligodendrocyte identity is crucial for subsequent events of myelination in the CNS. Here, we demonstrate that activation of ATP-dependent SWI/SNF chromatin-remodeling enzyme Smarca4/Brg1 at the differentiation onset is necessary and sufficient to initiate and promote oligodendrocyte lineage progression and maturation. Genome-wide multistage studies by ChIP-seq reveal that oligodendrocyte-lineage determination factor Olig2 functions as a prepatterning factor to direct Smarca4/Brg1 to oligodendrocyte-specific enhancers. Recruitment of Smarca4/Brg1 to distinct subsets of myelination regulatory genes is developmentally regulated. Functional analyses of Smarca4/Brg1 and Olig2 co-occupancy relative to chromatin epigenetic marking uncover stage-specific cis-regulatory elements that predict sets of transcriptional regulators controlling oligodendrocyte differentiation. Together, our results demonstrate that regulation of the functional specificity and activity of a Smarca4/Brg1-dependent chromatin-remodeling complex by Olig2, coupled with transcriptionally linked chromatin modifications, is critical to precisely initiate and establish the transcriptional program that promotes oligodendrocyte differentiation and subsequent myelination of the CNS. |
