TY - JOUR
T1 - Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage
AU - Lien, Wen Hui
AU - Guo, Xingyi
AU - Polak, Lisa
AU - Lawton, Lee N.
AU - Young, Richard A.
AU - Zheng, Deyou
AU - Fuchs, Elaine
N1 - Funding Information:
We thank S. Dewell for assistance in high-throughput sequencing and analysis (RU Genomics Resource Center); A. Viale, D. You, and J. Zhao for microarray (MSKCC microarray facility); S. Mazel, L. Li, A. Lloyd, and S. Tadesse for FACS sorting (RU FACS facility); and K.-M. Noh (Allis lab, RU) for providing ESC cDNAs. We also thank Fuchs' lab members N. Stokes and D. Oristian for assistance in mouse research (Fuchs lab); E. Ezhkova for Ezh1/2 dKO cDNA samples; Y.-C. Hsu for unpublished microarray information; and A. Folgueras, E. Ezhkova, L. Zhang, S. Beronja, B. Keyes, M. Kadaja, Y.-C. Hsu, and T. Chen for discussions and comments on the manuscript. W.-H.L. was supported by a Harvey L. Karp Postdoctoral Fellowship and is currently a Jane Coffin Child Postdoctoral Fellow. E.F. is an HHMI Investigator. This work was supported by a grant (to E.F.) from the NIH/NIAMS (R01AR31737) and partially by NIH/NIMH (R21MH087840, D.Z.).
PY - 2011/9/2
Y1 - 2011/9/2
N2 - 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.
AB - 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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U2 - 10.1016/j.stem.2011.07.015
DO - 10.1016/j.stem.2011.07.015
M3 - Article
C2 - 21885018
AN - SCOPUS:80052298366
SN - 1934-5909
VL - 9
SP - 219
EP - 232
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 3
ER -