Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage

Wen Hui Lien, Xingyi Guo, Lisa Polak, Lee N. Lawton, Richard A. Young, Deyou Zheng, Elaine Fuchs

Research output: Contribution to journalArticle

134 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)219-232
Number of pages14
JournalCell Stem Cell
Volume9
Issue number3
DOIs
StatePublished - Sep 2 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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