Genome-wide Maps of Histone Modifications Unwind In Vivo Chromatin States of the Hair Follicle Lineage

Lien, Wen-Hui;Guo, Xingyi;Polak, Lisa;Lawton, Lee N.;Fuchs, Elaine;et.al.
(2011) Cell Stem Cell — Vol. 9, n° 3, p. 219-232 (2011)

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Authors
  • Lien, Wen-Huiorcid-logoUCLouvain
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  • Guo, Xingyi
    Author
  • Polak, Lisa
    Author
  • Lawton, Lee N.
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  • Fuchs, Elaine
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Abstract
Using mouse skin, where bountiful reservoirs of synchronized hair follicle stem cells (HF-SCs) fuel cycles of regeneration, we explore how adult SCs remodel chromatin in response to activating cues. By profiling global mRNA and chromatin changes in quiescent and activated HF-SCs and their committed, transit-amplifying (TA) progeny, we show that polycomb-group (PcG)-mediated H3K27-trimethylation features prominently in HF-lineage progression by mechanisms distinct from embryonic-SCs. In HF-SCs, PcG represses nonskin lineages and HF differentiation. In TA progeny, nonskin regulators remain PcG-repressed, HF-SC regulators acquire H3K27me3-marks, and HF-lineage regulators lose them. Interestingly, genes poised in embryonic stem cells, active in HF-SCs, and PcG-repressed in TA progeny encode not only key transcription factors, but also signaling regulators. We document their importance in balancing HF-SC quiescence, underscoring the power of chromatin mapping in dissecting SC behavior. Our findings explain how HF-SCs cycle through quiescent and activated states without losing stemness and define roles for PcG-mediated repression in governing a fate switch irreversibly.
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Citations

Lien, W.-H., Guo, X., Polak, L., Lawton, Lee N., Young, Richard A., Zheng, D., & Fuchs, E. (2011). Genome-wide Maps of Histone Modifications Unwind In Vivo Chromatin States of the Hair Follicle Lineage. Cell Stem Cell, 9(3), 219-232. https://doi.org/10.1016/j.stem.2011.07.015 (Original work published 2011)