Genome-wide Maps of Histone Modifications Unwind In Vivo Chromatin States of the Hair Follicle Lineage
Author(s)Lien, Wen-Hui; Guo, Xingyi; Polak, Lisa; Lawton, Lee N.; Young, Richard A.; Zheng, Deyou; Fuchs, Elaine; ... Show more Show less
MetadataShow full item record
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.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Cell Stem Cell
Lien, Wen-Hui, Xingyi Guo, Lisa Polak, Lee N. Lawton, Richard A. Young, Deyou Zheng, and Elaine Fuchs. “Genome-Wide Maps of Histone Modifications Unwind In Vivo Chromatin States of the Hair Follicle Lineage.” Cell Stem Cell 9, no. 3 (September 2011): 219–232. © 2011 Elsevier Inc.
Final published version