Chromatin and Transcription Transitions of Mammalian Adult Germline Stem Cells and Spermatogenesis
Open accessAbstract
Adult germline stem cells (AGSCs) self-renew (Thy1(+) enriched) or commit to gametogenesis (Kit(+) enriched). To better understand how chromatin regulates AGSC biology and gametogenesis, we derived stage-specific high-resolution profiles of DNA methylation, 5hmC, histone modifications/variants, and RNA-seq in AGSCs and during spermatogenesis. First, we define striking signaling and transcriptional differences between AGSC types, involving key self-renewal and proliferation pathways. Second, key pluripotency factors (e.g., Nanog) are silent in AGSCs and bear particular chromatin/DNAme attributes that may "poise" them for reactivation after fertilization. Third, AGSCs display chromatin "poising/bivalency" of enhancers and promoters for embryonic transcription factors. Remarkably, gametogenesis occurs without significant changes in DNAme and instead involves transcription of DNA-methylated promoters bearing high RNAPol2, H3K9ac, H3K4me3, low CG content, and (often) 5hmC. Furthermore, key findings were confirmed in human sperm. Here, we reveal AGSC signaling asymmetries and chromatin/DNAme strategies in AGSCs to poise key transcription factors and to activate DNA-methylated promoters during gametogenesis.
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Many genes are expressed during spermatogenesis despite high methylation at their promoters.
“and numerous genes are expressed during spermatogenesis despite high level methylation at their promoters (18).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [18]
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- Authors
- Hammoud, S. S., Low, D. H. P., Yi, C., Carrell, D. T., Guccione, E., & Cairns, B. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Agency for Science, Technology and Research (SG)
- University of Utah (US)
- Corresponding author
- Guccione, Ernesto
- Cairns, Bradley R.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 15
- Issue
- 2
- Pages
- 239-253
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W1994950146
- Cited by
- 346
- References
- 46
- Citations by year
- 2026: 12 · 2025: 32 · 2024: 19 · 2023: 27 · 2022: 34 · 2021: 31 · 2020: 33 · 2019: 39 · 2018: 25 · 2017: 35 · 2016: 27 · 2015: 26 · 2014: 6
- FWCI
- 37.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (CA24014)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- 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
- spermatogenesis, chromatin regulation, DNA methylation, 5-hydroxymethylcytosine, histone modifications, histone variants, bivalent promoters, enhancers, Nanog, pluripotency factors, self-renewal, human spermatozoa
- MeSH terms
- Animals, Cell Differentiation, Cell Separation, Chromatin, Enhancer Elements, Genetic, Flow Cytometry, Histones, Humans, Male, Mice, Inbred C57BL, Promoter Regions, Genetic, Spermatogenesis, Spermatozoa, Time Factors, Transcription, Genetic, Signal Transduction, DNA Methylation, Gene Expression Profiling, Genomics, Mice, Embryonic Stem Cells, Adult Stem Cells
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