English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Rapid chromatin switch in the direct reprogramming of fibroblasts to neurons

MPS-Authors
/persons/resource/persons179767

Treutlein,  Barbara
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)
Supplementary Material (public)
There is no public supplementary material available
Citation

Wapinski, O. L., Lee, Q. Y., Chen, A. C., Li, R., Corces, M. R., Ang, C. E., et al. (2017). Rapid chromatin switch in the direct reprogramming of fibroblasts to neurons. Cell Reports, 20(13), 3236-3247. doi:10.1016/j.celrep.2017.09.011.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002D-FC6F-9
Abstract
Summary How transcription factors (TFs) reprogram one cell lineage to another remains unclear. Here, we define chromatin accessibility changes induced by the proneural TF Ascl1 throughout conversion of fibroblasts into induced neuronal (iN) cells. Thousands of genomic loci are affected as early as 12 hr after Ascl1 induction. Surprisingly, over 80% of the accessibility changes occur between days 2 and 5 of the 3-week reprogramming process. This chromatin switch coincides with robust activation of endogenous neuronal TFs and nucleosome phasing of neuronal promoters and enhancers. Subsequent morphological and functional maturation of iN cells is accomplished with relatively little chromatin reconfiguration. By integrating chromatin accessibility and transcriptome changes, we built a network model of dynamic TF regulation during iN cell reprogramming and identified Zfp238, Sox8, and Dlx3 as key TFs downstream of Ascl1. These results reveal a singular, coordinated epigenomic switch during direct reprogramming, in contrast to stepwise cell fate transitions in development.