The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
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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“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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Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
In silico prediction of protein-protein interactions in human macrophages
Souiai, O., Guerfali, F. Z., Miled, S. B., Brun, C., & Benkahla, A. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-157 · Cited by 10,785
Significance analysis of microarrays applied to the ionizing radiation response
Tusher, V. G., Tibshirani, R., & Chu, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091062498 · Cited by 10,568
The language of covalent histone modifications
Strahl, B. D., & Allis, C. D. (2000) · Nature · doi:10.1038/47412 · Cited by 8,679 · cited 1×
“Similar results were obtained with PHF8 (1-447) (Fig.”
ResultMaere, S., Heymans, K., & Kuiper, M. T. R. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti551 · Cited by 4,163
Histone modifications at human enhancers reflect global cell-type-specific gene expression
Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., Ye, Z., Lee, L. K., Stuart, R. K., Ching, C. W., et al. (2009) · Nature · doi:10.1038/nature07829 · Cited by 2,533 · cited 2×
“The great majority of PHF8-bound promoters overlapped with H3K4me3 (6) and H3K4me2 positive promoters, while very few harbored H4K20me1, H3K9me1/2, or H3K27me2 marks (Fig.”
BackgroundResult[9] TM4 Microarray Software Suite
Saeed, A. I., BHAGABATI, N. K., Braisted, J. C., Liang, W. P., Sharov, V., Howe, E., Li, J., Thiagarajan, M., White, J., & Quackenbush, J. F. (2006) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(06)11009-5 · Cited by 1,996
JmjC-domain-containing proteins and histone demethylation
Klose, R. J., Kallin, E. M., & Zhang, Y. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1945 · Cited by 1,290 · cited 1×
“A gradient for eluting trypsin-digested peptides was established with a time-varying solvent mixture ((min, % of solvent A): (15, 95), (50, 60), (70, 30), (75, 5)) and electrosprayed directly into the LTQ-MS inlet (source voltage, 1.”
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Items 401–450 of 450
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Abid, D., Murphy, K. E., Murphy, Z. C., Rahman, N. F., Getman, M. R., & Steiner, L. A. (2025) · Development · doi:10.1242/dev.204485
Wu, D.-Y., Qian, Y., Li, Z., Wang, Z., Zhang, X., Cheng, X., Xu, P., Zhang, D., & Liang, H.-Q. (2025) · Fundamental Research · doi:10.1016/j.fmre.2025.08.004
“…for the dynamic remodeling of H4K20me3, we analyzed the expression patterns of the known methyl-transferases for H4K20me3, KMT5B and KMT5C [ 15 ], along with the potential H4K20 methylation demethylases, KDM7A and KDM7B [ 17 , 18 ], across different stages of pre-implantation human embryos.”
InfluentialSingh, S., Hungyo, K., Hassan, S. S., & Uversky, V. N. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.21.689746
“Proteins such as PHF8 (histone demethylase), OPHN1 (Rho-GTPase signaling), and TENM1 (neuronal adhesion) further illustrate the functional breadth unified by shared compositional features [69, 70, 71].”
The epigenetic regulation of cell cycle and chromatin dynamic by sirtuins
Martínez‐Redondo, P. (2014) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Zhou, M., Yang, Z., 王丹波, Chen, P., & Zhang, Y. (2021) · Figshare · doi:10.6084/m9.figshare.13669317
Yu, L., Ji, T., Liao, W., Xu, Y., Fang, Y., Zhu, Q., Nie, J., & Yang, D. (2023) · Figshare · doi:10.6084/m9.figshare.22624210
Zhou, M., Yang, Z., 王丹波, Chen, P., & Zhang, Y. (2021) · Figshare · doi:10.6084/m9.figshare.13669311
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Herviou, L., Ovejero, S., Izard, F., Gadacha, O. K., Gourzonès, C., Bellanger, C., Smedt, E. D., Ma, A., Vincent, L., Cartron, G., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16633476
Yu, L., Ji, T., Liao, W., Xu, Y., Fang, Y., Zhu, Q., Nie, J., & Yang, D. (2023) · Figshare · doi:10.6084/m9.figshare.22624195
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Li, X., Li, J., Tan, Y., Samuelsson, A., Nguyen, V. B., Nair, R. V., Colombe, A., Grimm, D., Rosenfeld, M. G., & Kapiloff, M. S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.16.706249
Self-citationEpigenetic regulation of serine biosynthesis by PHF8 during neurogenesis
Artés, M. H., Iacobucci, S., Barallobre, M. J., Carballeira, P., Garcia‐Cajide, M., Pérez‐Venteo, A., Padilla, N., Viegas, B., Díaz-Vásquez, A., Nacht, A. S., et al. (2026) · EMBO Reports · doi:10.1038/s44319-026-00713-8
“These fi ndings are in line with previous observations in cancer cell lines (Asensio-Juan et al, 2012; Liu et al, 2010).”
InfluentialHistone Modifications in the Cell Cycle of C. elegans Embryogenesis: A Comparative Review
Azhar, A. A., & Mendoza, H. (2026) · Epigenomes · doi:10.3390/epigenomes10010015
“In terms of erasers of H4K20 methylation, PHF8 functions as an H4K20me1 demethylase, with a role in the cell cycle in addition to its capability of demethylating H3K9me1/2 and H3K27me2 [142–144].”
Li, X., Wang, Y., Kang, L., Zhu, H., Liu, Q., & Li, H. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1574236
“Non-SMC condensin II complex subunit G2 (NCAPG2) is component of the condensing II complex and is crucial for chromosome condensation and segregation during mitosis (12).”
Principes de la régulation des origines de réplication par la lysine méthyltransférase PR-Set7
Brustel, J. (2012) · theses.fr (ABES) · doi:10.70675/17a0939dz8c18z40adz9225z2e5931dd5bc7
Hocquet, C. (2018) · theses.fr (ABES) · doi:10.70675/bfcf9f26ze4d1z4c3az86d1z0d684417d4b5
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Lemaire, S. (2019) · theses.fr (ABES) · doi:10.70675/f23d8d55z764cz4603za028zf9f54d767039
Méthylation de H3K27 : régulation et rôle dans le cartilage articulaire
Allas, L. (2019) · theses.fr (ABES) · doi:10.70675/0b801552z0546z4765za411z263c0baf83ef
Catalytic activity of KMT5B promotes ciliogenesis without affecting global chromatin accessibility
Tait, J., Marthen, C., Hoelscher, B., Straub, T., Hsam, O., & Rupp, R. A. W. (2026) · Life Science Alliance · doi:10.26508/lsa.202503455
“PHF8 converts H4K20me1 into unme-thylated H4K20 (Liu et al, 2010; Qi et al, 2010), whereas RSBN1 has been shown to demethylate H4K20me2 (Brejc et al, 2017), and recently, hHR23b has been shown to have activity towards all H4K20me states in vitro (Cao et al, 2020).”
SIRT2 antagonizes MOF function during mitotic entry
Espinosa‐Alcantud, M., Sima, N., Fernández-Duran, I., Marazuela-Duque, A., Martínez-Cebrián, G., Guitart-Solanes, A., Gámez-García, A., Martínez‐Redondo, P., Bosch‐Presegué, L., Vázquez, B. N., et al. (2026) · Science Advances · doi:10.1126/sciadv.aeb2915
“It is also important to note that our evidence suggests that the interplay between SIRT2 and MOF in the regulation of H4K20me1 is not globally linked to gene expression but rather to a well-defined structural role in chromatin compaction and mitotic entry ( 12 ).”
InfluentialSuzuki, H., Mukai, S., Kato, Y., Sakashita, E., Endo, H., Nojima, H., & Yabuta, N. (2026) · Journal of Cell Science · doi:10.1242/jcs.264138
Janna, A., Grégoire, S., Chow, S., & Couture, J.-F. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-19001-8.00004-0
García, M. A., Fueyo, R., & Martínez‐Balbás, M. A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-443-19001-8.00013-1
BindingDB Entry 50034383: Lysine demethylases inhibitors.
BindingDB (2012) · UC San Diego · doi:10.7270/q2d50nfr
Marcon, E., Smiley, S., Turinsky, A. L., & Greenblatt, J. F. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7931-4_1
Metadata
- 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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