ZBTB33 binds unmethylated regions of the genome associated with actively expressed genes
Open accessAbstract
Background: DNA methylation and repressive histone modifications cooperate to silence promoters. One mechanism by which regions of methylated DNA could acquire repressive histone modifications is via methyl DNA-binding transcription factors. The zinc finger protein ZBTB33 (also known as Kaiso) has been shown in vitro to bind preferentially to methylated DNA and to interact with the SMRT/NCoR histone deacetylase complexes. We have performed bioinformatic analyses of Kaiso ChIP-seq and DNA methylation datasets to test a model whereby binding of Kaiso to methylated CpGs leads to loss of acetylated histones at target promoters. Results: Our results suggest that, contrary to expectations, Kaiso does not bind to methylated DNA in vivo but instead binds to highly active promoters that are marked with high levels of acetylated histones. In addition, our studies suggest that DNA methylation and nucleosome occupancy patterns restrict access of Kaiso to potential binding sites and influence cell type-specific binding. Conclusions: We propose a new model for the genome-wide binding and function of Kaiso whereby Kaiso binds to unmethylated regulatory regions and contributes to the active state of target promoters.
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Kaiso is not associated with highly methylated promoters in GM12878 lymphoblastoid cells or K562 human myeloid leukaemia cell lines.
“a different study discovered that Kaiso was not associated with highly methylated promoters in GM12878 lympho-blastoid cells or in K562 human myeloid leukaemia cell lines64.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [64]
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Cites
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072 · see citing works
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382 · see citing works
Functions of DNA methylation: islands, start sites, gene bodies and beyond
Jones, P. A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3230 · Cited by 6,061 · see citing works
The Role of Chromatin during Transcription
Li, B., Carey, M., & Workman, J. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.015 · Cited by 3,503 · see citing works
The accessible chromatin landscape of the human genome
Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., et al. (2012) · Nature · doi:10.1038/nature11232 · Cited by 2,679 · see citing works
ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia
Landt, S. G., Marinov, G. K., Kundaje, A., Kheradpour, P., Pauli, F., Batzoglou, S., Bernstein, B. E., Bickel, P., Brown, J. B., Cayting, P., et al. (2012) · Genome Research · doi:10.1101/gr.136184.111 · Cited by 2,033 · see citing works
Self-citationLi, G., Ruan, X., Auerbach, R. K., Sandhu, K. S., Zheng, M., Wang, P., Poh, H. M., Goh, Y., Lim, J., Zhang, J., et al. (2012) · Cell · doi:10.1016/j.cell.2011.12.014 · Cited by 1,232 · see citing works
Measuring reproducibility of high-throughput experiments
Li, Q., Brown, J. B., Huang, H., & Bickel, P. J. (2011) · The Annals of Applied Statistics · doi:10.1214/11-aoas466 · Cited by 1,008 · 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
Measuring reproducibility of high-throughput experiments
Li, Q., Brown, J. B., Huang, H., & Bickel, P. J. (2010) · UC Berkeley · Cited by 915 · see citing works
Wang, J., Zhuang, J., Iyer, S., Lin, X.-Y., Whitfield, T. W., Greven, M. C., Pierce, B. G., Dong, X., Kundaje, A. B., Cheng, Y., et al. (2012) · Genome Research · doi:10.1101/gr.139105.112 · Cited by 820 · see citing works
Quenneville, S., Verde, G., Corsinotti, A., Kapopoulou, A., Jakobsson, J., Offner, S., Baglivo, I., Pedone, P. V., Grimaldi, G., Riccio, A., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.032 · Cited by 606 · see citing works
The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor
Prokhortchouk, A., Hendrich, B., Jørgensen, H., Ruzov, A., Wilm, M., Georgiev, G., Bird, A., & Prokhortchouk, E. (2001) · Genes & Development · doi:10.1101/gad.198501 · Cited by 533 · see citing works
Insights from genomic profiling of transcription factors
Farnham, P. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2636 · Cited by 519 · see citing works
Self-citationGenome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules
Kelly, T. K., Liu, Y., Lay, F. D., Liang, G., Berman, B. P., & Jones, P. A. (2012) · Genome Research · doi:10.1101/gr.143008.112 · Cited by 455 · see citing works
Chromatin higher-order structures and gene regulation
Li, G., & Reinberg, D. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2011.01.022 · Cited by 454 · see citing works
Brinkman, A. B., Gu, H., Bartels, S. J. J., Zhang, Y., Matarese, F., Simmer, F., Marks, H., Bock, C., Gnirke, A., Meissner, A., et al. (2012) · Genome Research · doi:10.1101/gr.133728.111 · Cited by 413 · see citing works
N-CoR Mediates DNA Methylation-Dependent Repression through a Methyl CpG Binding Protein Kaiso
Yoon, H.-G., Chan, D. W., Reynolds, A. B., Qin, J., & Wong, J. (2003) · Molecular Cell · doi:10.1016/j.molcel.2003.08.008 · Cited by 408 · see citing works
A Family of Human Zinc Finger Proteins That Bind Methylated DNA and Repress Transcription
Filion, G. J. P., Zhenilo, S. V., Salozhin, S. V., Yamada, D., Prokhortchouk, E., & Defossez, P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.169-181.2006 · Cited by 357 · see citing works
Daniel, J. M. (2002) · Nucleic Acids Research · doi:10.1093/nar/gkf398 · Cited by 301 · see citing works
Controls of Nucleosome Positioning in the Human Genome
Gaffney, D. J., McVicker, G., Pai, A. A., Fondufe‐Mittendorf, Y. N., Lewellen, N., Michelini, K., Widom, J., Gilad, Y., & Pritchard, J. K. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003036 · Cited by 296 · see citing works
Statham, A. L., Robinson, M. D., Song, J. Z., Coolen, M. W., Stirzaker, C., & Clark, S. J. (2012) · Genome Research · doi:10.1101/gr.132076.111 · Cited by 201 · see citing works
E2F in vivo binding specificity: Comparison of consensus versus nonconsensus binding sitesPreprint
Rabinovich, A., Jin, V. X., Rabinovich, R., Xu, X., & Farnham, P. (2008) · Genome Research · doi:10.1101/gr.080622.108 · Cited by 129 · see citing works
Self-citationBuck-Koehntop, B. A., Stanfield, R. L., Ekiert, D. C., Martinez-Yamout, M. A., Dyson, H. J., Wilson, I. A., & Wright, P. E. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213726109 · Cited by 128 · see citing works
5-azacytidine treatment reorganizes genomic histone modification patterns
Komashko, V., & Farnham, P. (2010) · Epigenetics · doi:10.4161/epi.5.3.11409 · Cited by 122 · see citing works
Self-citationLopes, E. C., Valls, E., Figueroa, M. E., Mazur, A., Meng, F.-G., Chiosis, G., Laird, P. W., Schreiber-Agus, N., Greally, J. M., Prokhortchouk, E., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0344 · Cited by 119 · see citing works
Blahnik, K. R., Dou, L., O’Geen, H., McPhillips, T., Xu, X., Cao, A. R., Iyengar, S., Nicolet, C. M., Ludäscher, B., Korf, I. F., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1012 · Cited by 117 · see citing works
Self-citationA common mode of recognition for methylated CpG
Liu, Y., Zhang, X., Blumenthal, R., & Cheng, X. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.12.005 · Cited by 103 · see citing works
Lee, B., & Iyer, V. R. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.324962 · Cited by 95 · see citing works
Raghav, S. K., Waszak, S. M., Krier, I., Gubelmann, C., Isakova, A., Mikkelsen, T. S., & Deplancke, B. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.03.017 · Cited by 92 · see citing works
The Human Enhancer Blocker CTC-binding Factor Interacts with the Transcription Factor Kaiso
Defossez, P., Kelly, K. F., Filion, G. J. P., Pérez‐Torrado, R., Magdinier, F., Menoni, H., Nordgaard, C. L., Daniel, J. M., & Gilson, É. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510802200 · Cited by 87 · see citing works
Characterization of the Contradictory Chromatin Signatures at the 3′ Exons of Zinc Finger Genes
Blahnik, K. R., Dou, L., Echipare, L., Iyengar, S., O'Geen, H., Sánchez, E., Zhao, Y.-J., Marra, M., Hirst, M., Costello, J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017121 · Cited by 74 · see citing works
Self-citationDonaldson, N. S., Pierre, C. C., Anstey, M. I., Robinson, S. C., Weerawardane, S., & Daniel, J. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050398 · Cited by 56 · see citing works
Bartels, S. J. J., Spruijt, C. G., Brinkman, A. B., Jansen, P. W. T. C., Vermeulen, M., & Stunnenberg, H. G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025884 · Cited by 55 · see citing works
Nuclear import of the BTB/POZ transcriptional regulator Kaiso
Kelly, K. F., Otchere, A. A., Graham, M., & Daniel, J. M. (2004) · Journal of Cell Science · doi:10.1242/jcs.01541 · Cited by 53 · see citing works
The non-methylated DNA-binding function of Kaiso is not required in earlyXenopus laevisdevelopment
Ruzov, A. S., Savitskaya, E. E., Hackett, J. A., Reddington, J. P., Prokhortchouk, A., Madej, M. J., Chekanov, N., Li, M., Dunican, D. S., Prokhortchouk, E., et al. (2009) · Development · doi:10.1242/dev.025569 · Cited by 52 · see citing works
W-ChIPeaks: a comprehensive web application tool for processing ChIP-chip and ChIP-seq data
Lan, X., Bonneville, R., Apostolos, J., Wu, W., & Jin, V. X. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq669 · Cited by 45 · see citing works
Self-citationBuck‐Koehntop, B. A., Martinez‐Yamout, M. A., Dyson, H. J., & Wright, P. E. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.01.045 · Cited by 27 · see citing works
Kaiso regulates Znf131-mediated transcriptional activation
Donaldson, N. S., Nordgaard, C. L., Pierre, C. C., et al. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.03.011 · Cited by 23 · see citing works
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Zhu, H., Wang, G., & Qian, J. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.83 · Cited by 649 · see citing works
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Héberlé, É., & Bardet, A. F. (2019) · Essays in Biochemistry · doi:10.1042/ebc20190033 · Cited by 347 · see citing works
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Ernst, J., Melnikov, A., Zhang, X., Wang, L., Rogov, P., Mikkelsen, T. S., & Kellis, M. (2016) · Nature Biotechnology · doi:10.1038/nbt.3678 · Cited by 162 · see citing works
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- Authors
- Blattler, A., Yao, L., Wang, Y., Ye, Z., Jin, V. X., & Farnham, P. J.
- Affiliations
- University of Southern California (US)
- The Ohio State University (US)
- Corresponding author
- Farnham, Peggy J
- Venue
- Epigenetics & Chromatin
- Published
- 2013-05-21
- Volume
- 6
- Issue
- 1
- Pages
- 13-13
- ISSN
- 1756-8935 (ISSN-L)
- PMC
- PMC3663758
- OpenAlex
- W2152609389
- Cited by
- 82
- References
- 39
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 16 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 9 · 2018: 9 · 2017: 6 · 2016: 5 · 2015: 10 · 2014: 6 · 2013: 2
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Epigenetics & Chromatin (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (U54HG004558)
- National Cancer Institute (P30CA014089)
- 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 › Chromatin Remodeling and Cancer
- Keywords
- ZBTB33, Kaiso, DNA methylation, histone acetylation, transcription factor binding, nucleosome occupancy, cell type-specific binding, chromatin regulation
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