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Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice.
- Source :
- Nature; 5/21/2015, Vol. 521 Issue 7552, p366-370, 5p
- Publication Year :
- 2015
-
Abstract
- Adult stem cells occur in niches that balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, stem cells outside their niche often display fate flexibility. Here we show that super-enhancers underlie the identity, lineage commitment and plasticity of adult stem cells in vivo. Using hair follicle as a model, we map the global chromatin domains of hair follicle stem cells and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters ('epicentres') of transcription factor binding sites undergo remodelling upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, hair follicle stem cells dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicentres, enabling their genes to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation. [ABSTRACT FROM AUTHOR]
- Subjects :
- STEM cell research
CHROMATIN
CELL differentiation
TRANSCRIPTION factors
GENES
Subjects
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 521
- Issue :
- 7552
- Database :
- Complementary Index
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 102815110
- Full Text :
- https://doi.org/10.1038/nature14289