Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation.

Authors: Yu, Y  Chen, Y  Kim, B  Wang, H  Zhao, C  He, X  Liu, L  Liu, W  Wu, LM  Mao, M  Chan, JR  Wu, J  Lu, QR 
Citation: Yu Y, etal., Cell. 2013 Jan 17;152(1-2):248-61. doi: 10.1016/j.cell.2012.12.006.
Pubmed: (View Article at PubMed) PMID:23332759
DOI: Full-text: DOI:10.1016/j.cell.2012.12.006

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.

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RGD ID: 8554496
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.