Nucleosome-Interacting Proteins Regulated by DNA and Histone Methylation
Open accessAbstract
Modifications on histones or on DNA recruit proteins that regulate chromatin function. Here, we use nucleosomes methylated on DNA and on histone H3 in an affinity assay, in conjunction with a SILAC-based proteomic analysis, to identify "crosstalk" between these two distinct classes of modification. Our analysis reveals proteins whose binding to nucleosomes is regulated by methylation of CpGs, H3K4, H3K9, and H3K27 or a combination thereof. We identify the origin recognition complex (ORC), including LRWD1 as a subunit, to be a methylation-sensitive nucleosome interactor that is recruited cooperatively by DNA and histone methylation. Other interactors, such as the lysine demethylase Fbxl11/KDM2A, recognize nucleosomes methylated on histones, but their recruitment is disrupted by DNA methylation. These data establish SILAC nucleosome affinity purifications (SNAP) as a tool for studying the dynamics between different chromatin modifications and provide a modification binding "profile" for proteins regulated by DNA and histone methylation.
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As a cell ages, the methylation landscape changes dynamically.
“As a cell ages, the methylation landscape changes dynamically (Figure 2).”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [46]
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Cites
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · see citing works
Self-citationDignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262 · see citing works
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883 · see citing works
Self-citationCrystal structure of the nucleosome core particle at 2.8 Å resolution
Luger, K., Mäder, A. W., Richmond, R. K., Sargent, D. F., & Richmond, T. J. (1997) · Nature · doi:10.1038/38444 · Cited by 9,466 · see citing works
Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
Bannister, A. J., Zegerman, P., Partridge, J. F., Miska, E. A., Thomas, J. O., Allshire, R. C., & Kouzarides, T. (2001) · Nature · doi:10.1038/35065138 · Cited by 2,903 · see citing works
Self-citationHistone demethylation by a family of JmjC domain-containing proteins
Tsukada, Y.-I., Fang, J., Erdjument‐Bromage, H., Warren, M., Borchers, C. H., Tempst, P., & Zhang, Y. (2005) · Nature · doi:10.1038/nature04433 · Cited by 2,171 · see citing works
Bernstein, B. E., Meissner, A., & Lander, E. S. (2007) · Cell · doi:10.1016/j.cell.2007.01.033 · Cited by 2,086 · see citing works
Lowary, P. T., & Widom, J. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1494 · Cited by 1,782 · see citing works
Taverna, S. D., Li, H., Ruthenburg, A. J., Allis, C. D., & Patel, D. J. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1338 · Cited by 1,419 · see citing works
Multivalent engagement of chromatin modifications by linked binding modules
Ruthenburg, A. J., Li, H., Patel, D. J., & Allis, C. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2298 · Cited by 1,015 · see citing works
Reconstitution of Nucleosome Core Particles from Recombinant Histones and DNA
Dyer, P. N., Edayathumangalam, R. S., White, C. L., Bao, Y., Chakravarthy, S., Muthurajan, U. M., & Luger, K. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)75002-2 · Cited by 867 · see citing works
Vermeulen, M., Eberl, H. C., Matarese, F., Marks, H., Denissov, S., Butter, F., Lee, K. K., Olsen, J. V., Hyman, A. A., Stunnenberg, H. G., et al. (2010) · Cell · doi:10.1016/j.cell.2010.08.020 · Cited by 806 · see citing works
Self-citationA model for transmission of the H3K27me3 epigenetic mark
Hansen, K. H., Bracken, A. P., Pasini, D., Dietrich, N., Gehani, S. S., Monrad, A., Rappsilber, J., Lerdrup, M., & Helin, K. (2008) · Nature Cell Biology · doi:10.1038/ncb1787 · Cited by 720 · see citing works
Semisynthesis of Proteins by Expressed Protein Ligation
Muir, T. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161900 · Cited by 692 · see citing works
Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation
Pray-Grant, M. G., Daniel, J. A., Schieltz, D. M., Yates, J. R., & Grant, P. A. (2005) · Nature · doi:10.1038/nature03242 · Cited by 516 · see citing works
Neumann, H., Hancock, S. M., Buning, R., Routh, A. L., Chapman, L., Somers, J., Owen‐Hughes, T., van Noort, J., Rhodes, D., & Chin, J. W. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.07.027 · Cited by 498 · see citing works
The Site-Specific Installation of Methyl-Lysine Analogs into Recombinant Histones
Simon, M. D., Feixia Chu, C., Racki, L. R., de la Cruz, C. C., Burlingame, A. L., Panning, B., Narlikar, G. J., & Shokat, K. M. (2007) · Cell · doi:10.1016/j.cell.2006.12.041 · Cited by 475 · see citing works
Association of the Origin Recognition Complex with Heterochromatin and HP1 in Higher Eukaryotes
Pak, D. T. S., Pflumm, M. F., Chesnokov, I. N., Huang, D. W., Kellum, R., Marr, J., Romanowski, P., & Botchan, M. R. (1997) · Cell · doi:10.1016/s0092-8674(00)80415-8 · Cited by 408 · see citing works
Gearhart, M. D., Corcoran, C. M., Wamstad, J. A., & Bardwell, V. J. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00630-06 · Cited by 352 · see citing works
MBD2/NuRD and MBD3/NuRD, Two Distinct Complexes with Different Biochemical and Functional Properties
Le Guezennec, X., Vermeulen, M., Brinkman, A. B., Hoeijmakers, W. A. M., Cohen, A., Lasonder, E., & Stunnenberg, H. G. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.3.843-851.2006 · Cited by 340 · see citing works
Self-citationCpG Islands Recruit a Histone H3 Lysine 36 Demethylase
Blackledge, N. P., Zhou, J., Tolstorukov, M. Y., Farcas, A. M., Park, P. J., & Klose, R. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.04.009 · Cited by 310 · see citing works
Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance
Prasanth, S. G., Prasanth, K. V., Siddiqui, K., Spector, D. L., & Stillman, B. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600255 · Cited by 260 · see citing works
Karagianni, P., Amazit, L., Qin, J., & Wong, J. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01598-07 · Cited by 249 · see citing works
Kleine‐Kohlbrecher, D., Christensen, J. F., Vandamme, J., Abarrategui, I., Bak, M., Tommerup, N., Shi, X., Gozani, O., Rappsilber, J., Salcini, A. E., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.03.002 · Cited by 212 · see citing works
A new algorithm for hybrid hierarchical clustering with visualization and the bootstrap
van der Laan, M. J., & Pollard, K. S. (2003) · Journal of Statistical Planning and Inference · doi:10.1016/s0378-3758(02)00388-9 · Cited by 190 · see citing works
Genetically Encoding Nϵ-Methyl- l -lysine in Recombinant Histones
Nguyen, D., García-Alai, M., Kapadnis, P. B., Neumann, H., & Chin, J. W. (2009) · Journal of the American Chemical Society · doi:10.1021/ja906603s · Cited by 164 · see citing works
Frescas, D., Guardavaccaro, D., Kuchay, S., Kato, H., Poleshko, A. S., Basrur, V., Elenitoba‐Johnson, K. S. J., Katz, R. A., & Pagano, M. (2008) · Cell Cycle · doi:10.4161/cc.7.22.7062 · Cited by 136 · see citing works
Hashimoto, H., Horton, J. R., Zhang, X., & Cheng, X. (2009) · Epigenetics · doi:10.4161/epi.4.1.7370 · Cited by 124 · see citing works
A Native Peptide Ligation Strategy for Deciphering Nucleosomal Histone Modifications
Shogren‐Knaak, M. A., Fry, C. J., & Peterson, C. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301445200 · Cited by 116 · see citing works
JmjC enzyme KDM2A is a regulator of rRNA transcription in response to starvation
Tanaka, Y., Okamoto, K., Teye, K., Umata, T., Yamagiwa, N., Suto, Y., Zhang, Y., & Tsuneoka, M. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.56 · Cited by 113 · see citing works
A chromodomain switch mediated by histone H3 Lys 4 acetylation regulates heterochromatin assemblyPreprint
Xhemalçe, B., & Kouzarides, T. (2010) · Genes & Development · doi:10.1101/gad.1881710 · Cited by 101 · see citing works
Self-citationMany paths to one goal? The proteins that recognize methylated DNA in eukaryotes
Sasai, N., & Defossez, P. (2009) · The International Journal of Developmental Biology · doi:10.1387/ijdb.082652ns · Cited by 96 · see citing works
Zhao, Q., Qin, L., Jiang, F., Wu, B., Yue, W., Xu, F., Rong, Z., Yuan, H., Xie, X., Gao, Y., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604029200 · Cited by 65 · see citing works
Two Chromatin Remodeling Activities Cooperate during Activation of Hormone Responsive Promoters
Vicent, G. P., Zaurin, R., Nacht, A. S., Li, A., Font-Mateu, J., Le Dily, F., Vermeulen, M., Mann, M., & Beato, M. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000567 · Cited by 55 · see citing works
Self-citation
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Sorted by citations
Regulation of chromatin by histone modifications
Bannister, A. J., & Kouzarides, T. (2011) · Cell Research · doi:10.1038/cr.2011.22 · Cited by 6,012 · see citing works
Self-citationCancer epigenetics: from mechanism to therapy
Dawson, M. A., & Kouzarides, T. (2012) · Cell · doi:10.1016/j.cell.2012.06.013 · Cited by 3,203 · see citing works
Self-citationDNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045 · see citing works
A decade of exploring the cancer epigenome—biological and translational implications
Baylin, S. B., & Jones, P. A. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3130 · Cited by 2,871 · see citing works
Histone methylation: a dynamic mark in health, disease and inheritance
Greer, E. L., & Shi, Y. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3173 · Cited by 2,241 · see citing works
NF-κB, the first quarter-century: remarkable progress and outstanding questions
Hayden, M. S., & Ghosh, S. (2012) · Genes & Development · doi:10.1101/gad.183434.111 · Cited by 1,693 · see citing works
Pioneer transcription factors: establishing competence for gene expression
Zaret, K. S., & Carroll, J. S. (2011) · Genes & Development · doi:10.1101/gad.176826.111 · Cited by 1,589 · see citing works
Dynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives
Spruijt, C. G., Gnerlich, F., Smits, A. H., Pfaffeneder, T., Jansen, P. W. T. C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.02.004 · Cited by 973 · see citing works
Self-citationTranscription factors as readers and effectors of DNA methylation
Zhu, H., Wang, G., & Qian, J. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.83 · Cited by 649 · see citing works
The roles of DNA, RNA and histone methylation in ageing and cancer
Michalak, E. M., Burr, M. L., Bannister, A. J., & Dawson, M. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0143-1 · Cited by 549 · see citing works
Genome-wide Analysis Reveals TET- and TDG-Dependent 5-Methylcytosine Oxidation Dynamics
Shen, L., Wu, H., Diep, D., Yamaguchi, S., D’Alessio, A. C., Fung, H.-L., Zhang, K., & Zhang, Y. (2013) · Cell · doi:10.1016/j.cell.2013.04.002 · Cited by 497 · see citing works
DNA methylation presents distinct binding sites for human transcription factors
Hu, S., Wan, J., Su, Y., Song, Q., Zeng, Y., Nguyen, H. N., Shin, J., Cox, E., Rho, H. S., Woodard, C., et al. (2013) · eLife · doi:10.7554/elife.00726 · Cited by 349 · see citing works
Landan, G., Cohen, N. M., Mukamel, Z., Bar, A., Molchadsky, A., Brosh, R., Horn-Saban, S., Zalcenstein, D. A., Goldfinger, N., Zundelevich, A., et al. (2012) · Nature Genetics · doi:10.1038/ng.2442 · Cited by 305 · see citing works
Chen, L., Chen, K., Lavery, L. A., Baker, S. A., Shaw, C. A., Li, W., & Zoghbi, H. Y. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505909112 · Cited by 301 · see citing works
Histones: At the Crossroads of Peptide and Protein Chemistry
Müller, M. M., & Muir, T. W. (2015) · Chemical Reviews · doi:10.1021/cr5003529 · Cited by 247 · see citing works
Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification
Tessarz, P., Santos-Rosa, H., Robson, S. C., Sylvestersen, K. B., Nelson, C. J., Nielsen, M. L., & Kouzarides, T. (2014) · Nature · doi:10.1038/nature12819 · Cited by 243 · see citing works
Self-citationMechanisms regulating PRC2 recruitment and enzymatic activity
Holoch, D., & Margueron, R. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.04.003 · Cited by 201 · see citing works
Eberl, H. C., Spruijt, C. G., Kelstrup, C. D., Vermeulen, M., & Mann, M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.026 · Cited by 189 · see citing works
Self-citationNeri, F., Incarnato, D., Krepelova, A., Rapelli, S., Pagnani, A., Zecchina, R., Parlato, C., & Oliviero, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-8-r91 · Cited by 179 · see citing works
Varshney, D., Vavrova-Anderson, J., Oler, A. J., Cowling, V. H., Cairns, B. R., & White, R. J. (2015) · Nature Communications · doi:10.1038/ncomms7569 · Cited by 105 · see citing works
Gabriele, M., Lopez Tobon, A., D'Agostino, G., & Testa, G. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.12.013 · Cited by 103 · see citing works
South, P. F., Harmeyer, K. M., Serratore, N. D., & Briggs, S. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215768110 · Cited by 42 · see citing works
- Authors
- Bartke, T., Vermeulen, M., Xhemalce, B., Robson, S. C., Mann, M., & Kouzarides, T.
- Affiliations
- The Gurdon Institute (GB)
- Max Planck Society (DE)
- Corresponding author
- Kouzarides, Tony
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 143
- Issue
- 3
- Pages
- 470-484
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3640253
- OpenAlex
- W2021803200
- Cited by
- 611
- References
- 35
- Citations by year
- 2026: 24 · 2025: 20 · 2024: 25 · 2023: 24 · 2022: 32 · 2021: 42 · 2020: 29 · 2019: 37 · 2018: 28 · 2017: 50 · 2016: 50 · 2015: 41 · 2014: 48 · 2013: 63 · 2012: 52
- FWCI
- 20.96
- 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, 1020 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 (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Wellcome Trust (092096)
- Cancer Research UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- DNA methylation, histone methylation, H3K4, H3K9, H3K27, CpG methylation, chromatin modification, origin recognition complex, lysine demethylase, chromatin-binding proteins
- MeSH terms
- DNA-Binding Proteins, HeLa Cells, Histones, Humans, Methylation, Nucleosomes, Oxidoreductases, N-Demethylating, Staining and Labeling, CpG Islands, DNA Methylation, Proteomics, Chromatin Assembly and Disassembly, F-Box Proteins, Cell Line, Tumor, Origin Recognition Complex, Jumonji Domain-Containing Histone Demethylases
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