Genome-wide Maps of Histone Modifications Unwind In Vivo Chromatin States of the Hair Follicle Lineage
Open accessAbstract
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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Few genes are marked by bivalent domains in lineage-restricted quiescent HFSCs, unlike ES cells.
“In contrast to observations in ES cells, few genes are marked by bivalent domains in lineage-restricted, quiescent HFSCs61.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [61]
Epigenetic profiling of the H3K4me3 mark in quiescent HFSCs or quiescent MuSCs has revealed a number of genes marked by this permissive histone mark.
“Epigenetic profiling of the H3K4me3 mark in quiescent HFSCs or quiescent MuSCs (T.H.C and T.A.R, unpublished observations) has revealed a number of genes that are marked by this permissive histone mark61,62.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [61]
Many H3K4me3-rich genes in quiescent HFSCs or MuSCs are expressed at low levels.
“In support of the hypothesis that the quiescent state is poised for activation, many of these H3K4me3-rich genes (most of which are expressed at low levels) are functionally important for activation and proliferation.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [61]
Many H3K4me3-rich genes in quiescent HFSCs or MuSCs are functionally important for activation and proliferation.
“In support of the hypothesis that the quiescent state is poised for activation, many of these H3K4me3-rich genes (most of which are expressed at low levels) are functionally important for activation and proliferation.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [61]
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References 46 · Cited by 199
- Authors
- Lien, W.-H., Guo, X., Polak, L., Lawton, L. N., Young, R. A., Zheng, D., & Fuchs, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Albert Einstein College of Medicine (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Fuchs, Elaine
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 9
- Issue
- 3
- Pages
- 219-232
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC3166618
- OpenAlex
- W2101367152
- Cited by
- 199
- References
- 46
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 7 · 2022: 12 · 2021: 12 · 2020: 11 · 2019: 15 · 2018: 19 · 2017: 11 · 2016: 14 · 2015: 18 · 2014: 23 · 2013: 30 · 2012: 13
- FWCI
- 25.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 685 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (R21MH087840)
- National Human Genome Research Institute (R01HG002668)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR31737, R01AR031737)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- hair follicle stem cells, chromatin remodeling, histone modifications, H3K27me3, Polycomb group proteins, stem cell quiescence, skin regeneration, mouse skin
- MeSH terms
- Animals, Cell Differentiation, Histones, Protein Processing, Post-Translational, Repressor Proteins, Skin, Signal Transduction, Hair Follicle, Cell Lineage, Chromatin Assembly and Disassembly, Guided Tissue Regeneration, Mice, Adult Stem Cells, Genome-Wide Association Study, Polycomb-Group Proteins
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