PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.
Open accessAbstract
While reversible histone modifications are linked to an ever-expanding range of biological functions, the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while using multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1-S transition in conjunction with E2F1, HCF-1 (also known as HCFC1) and SET1A (also known as SETD1A), at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the condensin II loading process. Accordingly, the HEAT repeat clusters in two non-structural maintenance of chromosomes (SMC) condensin II subunits, N-CAPD3 and N-CAPG2 (also known as NCAPD3 and NCAPG2, respectively), are capable of recognizing H4K20me1, and ChIP-Seq analysis demonstrates a significant overlap of condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression.
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USP7 deubiquitinates and stabilizes PHF8, allowing PHF8 to upregulate gene targets involved in cell cycle progression, including cyclin A2.
“As we discussed in the Cell Cycle Regulation section, USP7 deubiquitinates and stabilizes PHF8, allowing the latter to upregulate gene targets involved in cell cycle progression, including cyclin A2 (Liu et al., 2010; Wang et al., 2016).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Liu et al., 2010
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- Authors
- Liu, W., Tanasa, B., Tyurina, O. V., Zhou, T. Y., Gassmann, R., Liu, W. T., Ohgi, K. A., Benner, C., Garcia-Bassets, I., Aggarwal, A. K., Desai, A., Dorrestein, P. C., Glass, C. K., & Rosenfeld, M. G.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California San Diego (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Rosenfeld, Michael G.
- ORCID
- Venue
- Nature
- Published
- 2010-07
- Volume
- 466
- Issue
- 7305
- Pages
- 508-512
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3059551
- OpenAlex
- W2130239280
- Cited by
- 441
- References
- 43
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 17 · 2023: 39 · 2022: 21 · 2021: 37 · 2020: 16 · 2019: 17 · 2018: 19 · 2017: 35 · 2016: 32 · 2015: 30 · 2014: 33 · 2013: 39 · 2012: 33
- FWCI
- 15.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Defense
- Howard Hughes Medical Institute
- National Institutes of Health
- University of California, San Diego
- National Heart, Lung, and Blood Institute (R01HL065445)
- National Cancer Institute (R01CA097134)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK039949, R37DK039949, R01DK018477)
- National Institute of Neurological Disorders and Stroke (R01NS034934)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- PHF8, H4K20me1, Jumonji C domain, cell cycle progression, G1/S transition, E2F1, HCF-1, SET1A, X-linked intellectual disability, craniofacial development, neuronal survival, histone demethylase, chromatin regulation, zebrafish, promoter recruitment
- MeSH terms
- Adenosine Triphosphatases, Cell Cycle, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, HeLa Cells, Histones, Humans, Lysine, Methylation, Phosphorylation, Promoter Regions, Genetic, Histone-Lysine N-Methyltransferase, Transcription Factors, Protein Structure, Tertiary, Multiprotein Complexes, Host Cell Factor C1, Histone Demethylases
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