Histone H3 Lysine 56 Acetylation Is Linked to the Core Transcriptional Network in Human Embryonic Stem Cells
Open accessAbstract
Lysine 56 acetylation in the helical core of histone H3 opens yeast chromatin and enables histone gene transcription, DNA replication, and DNA repair and prevents epigenetic silencing. While K56Ac is globally abundant in yeast and flies, its presence has been uncertain in mammals. We show here using mass spectrometry and genome-wide analyses that K56Ac is present in human embryonic stem cells (hESCs), overlapping strongly at active and inactive promoters with the binding of the key regulators of pluripotency, NANOG, SOX2, and OCT4. This includes also the canonical histone gene promoters and those for the hESC-specific microRNAs. K56Ac then relocates to developmental genes upon cellular differentiation. Thus the K56Ac state more accurately reflects the epigenetic differences between hESCs and somatic cells than other active histone marks such as H3 K4 trimethylation and K9 acetylation. These results suggest that K56Ac is involved in the human core transcriptional network of pluripotency.
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The observed decrease in H3K56Ac levels was not due to effects of DNA damage on cell-cycle distributions, as this histone mark is not cell cycle regulated.
“the observed decrease in H3K56Ac levels were not due to effects of DNA damage on cell-cycle distributions, as this histone mark is not cell cycle regulated20,35”
From Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining (2010) · cites this paper as [35]
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Cites
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714 · see citing works
Embryonic Stem Cell Lines Derived from Human Blastocysts
Thomson, J. A., Itskovitz‐Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998) · Science · doi:10.1126/science.282.5391.1145 · Cited by 15,947 · 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
Crystal 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
Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells
Boyer, L. A., Lee, T. I., Cole, M. F., Johnstone, S. E., Levine, S. S., Zucker, J. P., Guenther, M. G., Kumar, R. M., Murray, H. L., Jenner, R. G., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.020 · Cited by 4,505 · see citing works
Chen, X., Han, X., Yuan, P., Fang, F., Huss, M., Vega, V. B., Wong, E., Orlov, Y. L., Zhang, W., Jiang, J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.04.043 · Cited by 2,474 · see citing works
Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells
Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Levine, S. S., Kumar, R., Chevalier, B. S., Johnstone, S. E., Cole, M. F., Isono, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.043 · Cited by 2,238 · see citing works
A Chromatin Landmark and Transcription Initiation at Most Promoters in Human Cells
Guenther, M. G., Levine, S. S., Boyer, L. A., Jaenisch, R., & Young, R. A. (2007) · Cell · doi:10.1016/j.cell.2007.05.042 · Cited by 1,946 · see citing works
Stem Cells, the Molecular Circuitry of Pluripotency and Nuclear Reprogramming
Jaenisch, R., & Young, R. A. (2008) · Cell · doi:10.1016/j.cell.2008.01.015 · Cited by 1,408 · see citing works
Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells
Marson, A., Levine, S. S., Cole, M. F., Frampton, G. M., Brambrink, T., Johnstone, S. E., Guenther, M. G., Johnston, W. K., Wernig, M., Newman, J. J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.020 · Cited by 1,361 · see citing works
Chromatin signatures of pluripotent cell lines
Azuara, V., Perry, P., Sauer, S., Spivakov, M., Jørgensen, H. F., John, R. M., Gouti, M., Casanova, M., Warnes, G., Merkenschlager, M., et al. (2006) · Nature Cell Biology · doi:10.1038/ncb1403 · Cited by 1,357 · see citing works
An Extended Transcriptional Network for Pluripotency of Embryonic Stem Cells
Kim, J., Chu, J., Shen, X., Wang, J., & Orkin, S. H. (2008) · Cell · doi:10.1016/j.cell.2008.02.039 · Cited by 1,321 · see citing works
The Histone Variant H3.3 Marks Active Chromatin by Replication-Independent Nucleosome Assembly
Ahmad, K., & Henikoff, S. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00542-7 · Cited by 1,117 · see citing works
Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
Initiative, T. I. S. C. (2007) · Nature Biotechnology · doi:10.1038/nbt1318 · Cited by 1,078 · see citing works
Human embryonic stem cells express a unique set of microRNAs
Suh, M. R., Lee, Y., Kim, J. Y., Kim, S.-K., Moon, S., Lee, J. Y., Cha, K., Chung, H., Yoon, H. S., Moon, S. Y., et al. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.02.019 · Cited by 974 · see citing works
Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells
Pan, G., Tian, S., Nie, J., Yang, C., Ruotti, V., Wei, H., Jonsdottir, G. A., Stewart, R., & Thomson, J. A. (2007) · Cell Stem Cell · doi:10.1016/j.stem.2007.08.003 · Cited by 711 · see citing works
A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response
Masumoto, H., Hawke, D. H., Kobayashi, R., & Verreault, A. (2005) · Nature · doi:10.1038/nature03714 · Cited by 595 · see citing works
Self-renewal of teratocarcinoma and embryonic stem cells
Chambers, I., & Smith, A. G. (2004) · Oncogene · doi:10.1038/sj.onc.1207930 · Cited by 535 · see citing works
Molecular signature of human embryonic stem cells and its comparison with the mouse
Sato, N., Muñoz-Sanjuán, I., Heke, M., Uchida, M., Naef, F., & Brivanlou, A. H. (2003) · Developmental Biology · doi:10.1016/s0012-1606(03)00256-2 · Cited by 469 · see citing works
The Human and Mouse Replication-Dependent Histone Genes
Marzluff, W. F., Gongidi, P., Woods, K., Jin, J., & Maltais, L. J. (2002) · Genomics · doi:10.1006/geno.2002.6850 · Cited by 461 · see citing works
Acetylation in Histone H3 Globular Domain Regulates Gene Expression in Yeast
Xu, F., Zhang, K., & Grunstein, M. R. (2005) · Cell · doi:10.1016/j.cell.2005.03.011 · Cited by 394 · see citing works
Self-citationChemical derivatization of histones for facilitated analysis by mass spectrometry
Garcia, B. A., Mollah, S., Ueberheide, B. M., Busby, S. A., Muratore‐Schroeder, T. L., Shabanowitz, J., & Hunt, D. F. (2007) · Nature Protocols · doi:10.1038/nprot.2007.106 · Cited by 389 · see citing works
Self-citationHyslop, L., Stojković, M., Armstrong, L., Walter, T., Stojković, P., Przyborski, S. A., Herbert, M., Murdoch, A. P., Strachan, T., & Lako, M. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0080 · Cited by 383 · see citing works
Recent advances in understanding chromatin remodeling by Swi/Snf complexes
Martens, J. A., & Winston, F. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(03)00022-4 · Cited by 352 · see citing works
Short-term BMP-4 treatment initiates mesoderm induction in human embryonic stem cells
Zhang, P., Li, J., Tan, Z., Wang, C., Liu, T., Chen, L., Yong, J., Jiang, W., Sun, X., Du, L., et al. (2007) · Blood · doi:10.1182/blood-2007-02-074120 · Cited by 319 · see citing works
Organismal Differences in Post-translational Modifications in Histones H3 and H4
Garcia, B. A., Hake, S. B., Diaz, R. L., Kauer, M., Morris, S. A., Recht, J., Shabanowitz, J., Mishra, N., Strahl, B. D., Allis, C. D., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607900200 · Cited by 314 · see citing works
Self-citationRufiange, A., Jacques, P.-É., Bhat, W., Robert, F., & Nourani, A. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.07.011 · Cited by 313 · see citing works
Unique gene expression signatures of independently-derived human embryonic stem cell lines
Abeyta, M. J., Clark, A. T., Rodriguez, R. T., Bodnar, M. S., Pera, R. A. R., & Firpo, M. T. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh068 · Cited by 285 · see citing works
Self-citationIdentification of novel histone post-translational modifications by peptide mass fingerprinting
Zhang, L., Eugeni, E. E., Parthun, M. R., & Freitas, M. A. (2003) · Chromosoma · doi:10.1007/s00412-003-0244-6 · Cited by 274 · see citing works
Kaeser, M. D., Aslanian, A., Dong, M., Yates, J. R., & Emerson, B. M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806061200 · Cited by 237 · see citing works
Williams, S. K., Truong, D. M., & Tyler, J. K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800057105 · Cited by 218 · see citing works
Wei, C. L., Miura, T., Robson, P., Lim, S. K., Xu, X., Lee, M. Y., Gupta, S. M., Stanton, L. W., Luo, Y., Schmitt, J., et al. (2005) · Stem Cells · doi:10.1634/stemcells.2004-0162 · Cited by 212 · see citing works
Laurent, L. C., Chen, J., Ulitsky, I., Müeller, F.-J., Lu, C., Ron Shamir, A., Fan, J., & Loring, J. F. (2008) · Stem Cells · doi:10.1634/stemcells.2007-1081 · Cited by 211 · see citing works
Adenovirus Small e1a Alters Global Patterns of Histone Modification
Horwitz, G. A., Zhang, K., McBrian, M. A., Grunstein, M. R., Kurdistani, S. K., & Berk, A. J. (2008) · Science · doi:10.1126/science.1155544 · Cited by 209 · see citing works
Self-citationRtt109 Is Required for Proper H3K56 Acetylation
Schneider, J., Bajwa, P., Johnson, F. C., Bhaumik, S. R., & Shilatifard, A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.c600265200 · Cited by 209 · see citing works
Sir2 Deacetylates Histone H3 Lysine 56 to Regulate Telomeric Heterochromatin Structure in Yeast
Xu, F., Zhang, Q., Zhang, K., Xie, W., & Grunstein, M. R. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.07.021 · Cited by 161 · see citing works
Self-citationMPSS profiling of human embryonic stem cells
Brandenberger, R., Khrebtukova, I., Thies, R. S., Miura, T., Cai, J., Puri, R. K., Vasicek, T., LEBKOWSKI, J. S., & Rao, M. S. (2004) · BMC Developmental Biology · doi:10.1186/1471-213x-4-10 · Cited by 139 · see citing works
Characterization of Lysine 56 of Histone H3 as an Acetylation Site in Saccharomyces cerevisiae
Özdemir, A., Spicuglia, S., Lasonder, E., Vermeulen, M., Campsteijn, C., Stunnenberg, H. G., & Logie, C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500181200 · Cited by 119 · see citing works
Reprogramming somatic cells towards pluripotency by defined factors
Lewitzky, M., & Yamanaka, S. (2007) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2007.09.007 · Cited by 109 · see citing works
Retinoic acid and homeobox gene regulation
Langston, A. W., & Gudas, L. J. (1994) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(94)90071-a · Cited by 100 · see citing works
Searching Chromatin for Stem Cell Identity
Buszczak, M., & Spradling, A. C. (2006) · Cell · doi:10.1016/j.cell.2006.04.004 · Cited by 99 · see citing works
Holmes, W. F., Braastad, C. D., Mitra, P., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506995200 · Cited by 53 · see citing works
Histone H3 K56 acetylation, chromatin assembly, and the DNA damage checkpoint
Downs, J. A. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.08.016 · Cited by 48 · see citing works
Miller, A., Yang, B., Foster, T., & Kirchmaier, A. L. (2008) · Genetics · doi:10.1534/genetics.107.084525 · Cited by 47 · see citing works
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Sebastián, C., Zwaans, B. M. M., Silberman, D. M., Gymrek, M., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A. R., Toiber, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.047 · Cited by 660 · see citing works
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining
Miller, K. M., Tjeertes, J. V., Coates, J., Legube, G., Polo, S. E., Britton, S., & Jackson, S. P. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1899 · Cited by 629 · see citing works
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Tjeertes, J. V., Miller, K. M., & Jackson, S. P. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.119 · Cited by 347 · see citing works
Sridharan, R., Gonzales-Cope, M., Chronis, C., Bonora, G., McKee, R., Huang, C., Patel, S., Lopez, D., Mishra, N., Pellegrini, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2768 · Cited by 220 · see citing works
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Wurtele, H., Tsao, S., Lépine, G., Mullick, A., Tremblay, J., Drogaris, P., Lee, E.-H., Thibault, P., Verreault, A., & Raymond, M. (2010) · Nature Medicine · doi:10.1038/nm.2175 · Cited by 157 · see citing works
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Su, D., Hu, Q., Li, Q., Thompson, J. R., Cui, G., Fazly, A., Davies, B. A., Botuyan, M. V., Zhang, Z., & Mer, G. (2012) · Nature · doi:10.1038/nature10861 · Cited by 128 · see citing works
Wu, H.-T., Kuo, Y.-C., Hung, J.-J., Huang, C.-H., Chen, W.-Y., Chou, T.-Y., Chen, Y., Chen, Y.-J., Chen, Y.-J., Cheng, W.-C., et al. (2016) · Nature Communications · doi:10.1038/ncomms13644 · Cited by 129 · see citing works
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- Authors
- Xie, W., Song, C., Young, N. L., Sperling, A. S., Xu, F., Sridharan, R., Conway, A. E., Garcia, B. A., Plath, K., Clark, A. T., & Grunstein, M.
- Affiliations
- University of California, Los Angeles (US)
- Princeton University (US)
- Corresponding author
- Clark, Amander T.
- Grunstein, Michael
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 33
- Issue
- 4
- Pages
- 417-427
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC2671231
- OpenAlex
- W1992111383
- Cited by
- 197
- References
- 44
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 3 · 2021: 11 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 4 · 2016: 13 · 2015: 12 · 2014: 17 · 2013: 17 · 2012: 19
- FWCI
- 10.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R37GM023674, R01GM023674)
- 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 › Pluripotent Stem Cells Research
- Keywords
- histone H3 lysine 56 acetylation, human embryonic stem cells, pluripotency, Nanog, SOX2, Oct4, histone gene transcription, histone acetylation, epigenetic regulation, transcriptional regulatory networks, cell differentiation, microRNA promoters, H3K4 trimethylation, H3K9 acetylation
- MeSH terms
- Nanog Homeobox Protein, Acetylation, Animals, Histones, Humans, Lysine, Protein Processing, Post-Translational, Genome, Human, Homeodomain Proteins, Chromatin Immunoprecipitation, Octamer Transcription Factor-3, Mice, Gene Regulatory Networks, Embryonic Stem Cells, SOXB1 Transcription Factors
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