N-CoR Mediates DNA Methylation-Dependent Repression through a Methyl CpG Binding Protein Kaiso
Open accessAbstract
The identification and characterization of molecular mechanisms utilized by cells to mediate transcriptional repression at methylated loci are fundamental to understanding the biological consequences of DNA methylation. Here we demonstrate that Kaiso, a methyl CpG binding protein belonging to the BTB/POZ family of transcription factors, is a component of the human N-CoR complex. In vitro, the Kaiso/N-CoR complex binds specific CpG-rich sequences in a methylation-dependent manner. In vivo, Kaiso targets the N-CoR complex to the MTA2 gene promoter in a methylation-dependent manner. Importantly, we demonstrate that Kaiso is required for transcriptional repression of the methylated MTA2 locus. Furthermore, this repression also requires a functional N-CoR deacetylase complex, which brings about histone hypoacetylation and methylation of H3 lysine 9 to the MTA2 locus. Thus, our data demonstrate a critical role for a methyl CpG binding protein in mediating DNA methylation-dependent repression and reveal the mechanism by which it represses transcription.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Cites
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756 · see citing works
DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124 · see citing works
Okano, M., Bell, D. W., Haber, D. A., & Li, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81656-6 · Cited by 6,143 · see citing works
Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.
Herman, J. G., Graff, J. R., Myöhänen, S., Nelkin, B. D., & Baylin, S. B. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9821 · Cited by 5,610 · see citing works
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality
Li, E., Bestor, T. H., & Jaenisch, R. (1992) · Cell · doi:10.1016/0092-8674(92)90611-f · Cited by 3,984 · see citing works
Nan, X., Ng, H.-H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N., & Bird, A. (1998) · Nature · doi:10.1038/30764 · Cited by 3,440 · see citing works
Regulation of chromatin structure by site-specific histone H3 methyltransferases
Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B. D., Sun, Z.-W., Schmid, M., Opravil, S., Mechtler, K., Ponting, C. P., Allis, C. D., et al. (2000) · Nature · doi:10.1038/35020506 · Cited by 2,845 · see citing works
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
Jones, P. L., Veenstra, G. J. C., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., & Wolffe, A. P. (1998) · Nature Genetics · doi:10.1038/561 · Cited by 2,734 · see citing works
The coregulator exchange in transcriptional functions of nuclear receptors
Glass, C. K., & Rosenfeld, M. G. (2000) · Genes & Development · doi:10.1101/gad.14.2.121 · Cited by 2,233 · see citing works
The DNA methyltransferases of mammals
Bestor, T. H. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.16.2395 · Cited by 2,045 · see citing works
Hörlein, A., Näär, A. M., Heinzel, T., Torchia, J., Gloss, B. R., Kurokawa, R., Ryan, A. K., Kamei, Y., Söderström, M., Glass, C. K., et al. (1995) · Nature · doi:10.1038/377397a0 · Cited by 2,035 · see citing works
Cameron, E. E., Bachman, K. E., Myöhänen, S., Herman, J. G., & Baylin, S. B. (1999) · Nature Genetics · doi:10.1038/5047 · Cited by 1,857 · see citing works
Methylation-Induced Repression— Belts, Braces, and Chromatin
Bird, A. P., & Wolffe, A. P. (1999) · Cell · doi:10.1016/s0092-8674(00)81532-9 · Cited by 1,827 · see citing works
A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome
Guy, J., Hendrich, B., Holmes, M., Martin, J. E., & Bird, A. (2001) · Nature Genetics · doi:10.1038/85899 · Cited by 1,558 · see citing works
Identification and Characterization of a Family of Mammalian Methyl-CpG Binding Proteins
Hendrich, B., & Bird, A. P. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.11.6538 · Cited by 1,352 · see citing works
Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice
Chen, R. Z., Akbarian, S., Tudor, M., & Jaenisch, R. (2001) · Nature Genetics · doi:10.1038/85906 · Cited by 1,275 · see citing works
Analysis of gene function in somatic mammalian cells using small interfering RNAs
Elbashir, S. M. (2002) · Methods · doi:10.1016/s1046-2023(02)00023-3 · Cited by 1,094 · see citing works
The Methyl-CpG-binding Protein MeCP2 Links DNA Methylation to Histone Methylation
Fuks, F., Hurd, P. J., Wolf, D., Nan, X., Bird, A. P., & Kouzarides, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210256200 · Cited by 994 · see citing works
MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex
Ng, H., Zhang, Y., Hendrich, B., Johnson, C. A., Turner, B. M., Erdjument‐Bromage, H., Tempst, P., Reinberg, D., & Bird, A. P. (1999) · Nature Genetics · doi:10.1038/12659 · Cited by 936 · see citing works
Histone methylation in transcriptional control
Kouzarides, T. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00287-3 · Cited by 908 · see citing works
Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation
Wade, P. A., Gégonne, A., Jones, P. L., Ballestar, E., Aubry, F., & Wolffe, A. P. (1999) · Nature Genetics · doi:10.1038/12664 · Cited by 811 · see citing works
Shahbazian, M. D., Young, J. I., Yuva‐Paylor, L. A., Spencer, C. M., Antalffy, B. A., Noebels, J. L., Armstrong, D. L., Paylor, R. E., & Zoghbi, H. Y. (2002) · Neuron · doi:10.1016/s0896-6273(02)00768-7 · Cited by 760 · see citing works
Both corepressor proteins SMRT and N‐CoR exist in large protein complexes containing HDAC3
Li, J., Wang, J., Wang, J., Nawaz, Z., Liu, J. M., Qin, J., & Wong, J. (2000) · The EMBO Journal · doi:10.1093/emboj/19.16.4342 · Cited by 629 · see citing works
Self-citationCombinatorial roles of the nuclear receptor corepressor in transcription and development.
Jepsen, K., Hermanson, O., Onami, T. M., Gleiberman, A., Lunyak, V., Mcevilly, R., Kurokawa, R., Kumar, V., Liu, F. C., Seto, E., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)00064-7 · Cited by 545 · 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
A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness
Guenther, M. G., Lane, W. S., Fischle, W., Verdin, E., Lazar, M. A., & Shiekhattar, R. (2000) · Genes & Development · doi:10.1101/gad.14.9.1048 · Cited by 489 · see citing works
Yoon, H., Chan, D. W., Huang, Z., Li, J., Fondell, J. D., Qin, J., & Wong, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg120 · Cited by 444 · see citing works
Self-citationZhang, J., Kalkum, M., Chait, B. T., & Roeder, R. G. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00468-9 · Cited by 414 · see citing works
Ballestar, E., & Wolffe, A. P. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.01869.x · Cited by 408 · see citing works
The Catenin p120 ctn Interacts with Kaiso, a Novel BTB/POZ Domain Zinc Finger Transcription Factor
Daniel, J. M., & Reynolds, A. B. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3614 · Cited by 406 · see citing works
Self-citationDNA methylation directs a time-dependent repression of transcription initiation
Kass, S. U., Landsberger, N., & Wolffe, A. P. (1997) · Current Biology · doi:10.1016/s0960-9822(97)70086-1 · Cited by 370 · see citing works
Dann, C. T., Subramaniam, K., Dunn, M. A., & Seydoux, G. (2001) · Genes & Development · doi:10.1101/gad.876201 · Cited by 357 · see citing works
Biological roles and mechanistic actions of co-repressor complexes
Jepsen, K., & Rosenfeld, M. G. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.4.689 · Cited by 316 · see citing works
N-CoR controls differentiation of neural stem cells into astrocytes
Hermanson, O., Jepsen, K., & Rosenfeld, M. G. (2002) · Nature · doi:10.1038/nature01156 · Cited by 308 · see citing works
Daniel, J. M. (2002) · Nucleic Acids Research · doi:10.1093/nar/gkf398 · Cited by 301 · see citing works
Active Repression of Methylated Genes by the Chromosomal Protein MBD1
Ng, H., Jeppesen, P., & Bird, A. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.4.1394-1406.2000 · Cited by 292 · see citing works
Altered methylation patterns in cancer cell genomes: Cause or consequence?
Baylin, S. B., & Bestor, T. H. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00061-2 · Cited by 280 · see citing works
Methyl CpG binding proteins: coupling chromatin architecture to gene regulation
Wade, P. A. (2001) · Oncogene · doi:10.1038/sj.onc.1204340 · Cited by 196 · see citing works
Unique forms of human and mouse nuclear receptor corepressor SMRT.
Ordentlich, P., Downes, M., Xie, W., Genin, A., Spinner, N., & Evans, R. (1999) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.96.6.2639 · Cited by 183 · see citing works
Tenenhaus, C. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/9024-dx23 · Cited by 150 · see citing works
Li, J., Lin, Q., Yoon, H., Huang, Z.-Q., Strahl, B. D., Allis, C. D., & Wong, J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.16.5688-5697.2002 · Cited by 141 · see citing works
Self-citationPark, E.-J., Schroen, D. J., Yang, M., Li, H. Z., Li, L., & Chen, J. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3519 · Cited by 129 · see citing works
Oncogenes and tumor suppressors in the molecular pathogenesis of acute promyelocytic leukemia
Pandolfi, P. P. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.7.769 · Cited by 108 · see citing works
Lorincz, M. C., Schübeler, D., & Groudine, M. T. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.23.7913-7922.2001 · Cited by 97 · see citing works
A Strategy for Rapid, High-Confidence Protein Identification
Qin, J., Fenyö, D., Zhao, Y., Hall, W. W., Chao, D. M., Wilson, C. J., Young, R. A., & Chait, B. T. (1997) · Analytical Chemistry · doi:10.1021/ac970488v · Cited by 90 · see citing works
Self-citationCorepressors and Nuclear Hormone Receptor Function
Ordentlich, P., Downes, M., & Evans, R. M. (2001) · Current topics in microbiology and immunology · doi:10.1007/978-3-662-10595-5_5 · Cited by 76 · see citing works
AR Possesses an Intrinsic Hormone-Independent Transcriptional Activity
Huang, Z., Li, J., & Wong, J. (2002) · Molecular Endocrinology · doi:10.1210/mend.16.5.0829 · Cited by 41 · see citing works
Self-citationMolecular Mechanisms of Corepressor Function
Urnov, F. D., Wolffe, A. P., & Guschin, D. Y. (2001) · Current topics in microbiology and immunology · doi:10.1007/978-3-662-10595-5_1 · Cited by 23 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
DNA methylation and its basic function
Moore, L. D., Le, T., & Fan, G. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.112 · Cited by 4,906 · see citing works
Rosenfeld, M. G., Lunyak, V. V., & Glass, C. K. (2006) · Genes & Development · doi:10.1101/gad.1424806 · Cited by 952 · see citing works
Sequence and structural analysis of BTB domain proteins
Stogios, P. J., Downs, G. S., Jauhal, J. J., Nandra, S. K., & Privé, G. G. (2005) · Genome Biology · doi:10.1186/gb-2005-6-10-r82 · Cited by 694 · see citing works
Transcription 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
Deconstructing repression: evolving models of co-repressor action
Perissi, V., Jepsen, K., Glass, C. K., & Rosenfeld, M. G. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2736 · Cited by 532 · see citing works
Retinoic acid receptors: From molecular mechanisms to cancer therapy
di Masi, A., Leboffe, L., De Marinis, E., Pagano, F., Cicconi, L., Rochette-Egly, C., Lo-Coco, F., Ascenzi, P., & Nervi, C. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.12.003 · Cited by 403 · see citing works
Rett syndrome: a neurological disorder with metabolic components
Kyle, S. M., Vashi, N., & Justice, M. J. (2018) · Open Biology · doi:10.1098/rsob.170216 · Cited by 213 · see citing works
Role of BDNF epigenetics in activity-dependent neuronal plasticity
Karpova, N. N. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.002 · Cited by 200 · see citing works
Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery
Oberoi, J., Fairall, L., Watson, P. J., Yang, J.-C., Czimmerer, Z., Kampmann, T., Goult, B. T., Greenwood, J. A., Gooch, J. T., Kallenberger, B. C., et al. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1983 · Cited by 165 · see citing works
Buck-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
Lopes, 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
ZBTB33 binds unmethylated regions of the genome associated with actively expressed genes
Blattler, A., Yao, L., Wang, Y., Ye, Z., Jin, V. X., & Farnham, P. J. (2013) · Epigenetics & Chromatin · doi:10.1186/1756-8935-6-13 · Cited by 82 · see citing works
Papoutsis, A. J., Selmin, O. I., Borg, J. L., & Romagnolo, D. F. (2015) · Molecular Carcinogenesis · doi:10.1002/mc.22095 · Cited by 79 · see citing works
Jessen, H. M., Kolodkin, M. H., Bychowski, M. E., Auger, C. J., & Auger, A. P. (2010) · Endocrinology · doi:10.1210/en.2009-0594 · Cited by 53 · see citing works
Piazza, R., Magistroni, V., Mogavero, A., Andreoni, F., Ambrogio, C., Chiarle, R., Mologni, L., Bachmann, P. S., Lock, R. B., Collini, P., et al. (2013) · Neoplasia · doi:10.1593/neo.121784 · Cited by 51 · see citing works
HDAC3 functions as a positive regulator in Notch signal transduction
Ferrante, F., Giaimo, B. D., Bartkuhn, M., Zimmermann, T., Close, V., Mertens, D., Nist, A., Stiewe, T., Meier-Soelch, J., Kracht, M., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa088 · Cited by 50 · see citing works
Jing, Y.-P., Liu, W., Wang, J.-X., & Zhao, X.-F. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.622696 · Cited by 30 · see citing works
- Authors
- Yoon, H.-G., Chan, D. W., Reynolds, A. B., Qin, J., & Wong, J.
- Affiliations
- Baylor College of Medicine (US)
- Vanderbilt University (US)
- Corresponding author
- Wong, Jiemin
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 12
- Issue
- 3
- Pages
- 723-734
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2085995080
- Cited by
- 408
- References
- 48
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 19 · 2023: 11 · 2022: 21 · 2021: 12 · 2020: 11 · 2019: 13 · 2018: 11 · 2017: 9 · 2016: 21 · 2015: 16 · 2014: 18 · 2013: 26 · 2012: 33
- FWCI
- 8.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 58679, R01DK056324, R01DK058679, DK 56324)
- 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
- Kaiso, methyl-CpG binding proteins, DNA methylation, transcriptional repression, histone deacetylase, histone H3 lysine 9 methylation, histone hypoacetylation, chromatin regulation
- MeSH terms
- Animals, Carrier Proteins, DNA-Binding Proteins, Eukaryotic Cells, Genes, Regulator, HeLa Cells, Histone Deacetylases, Histones, Humans, Lysine, Nuclear Proteins, Promoter Regions, Genetic, Repressor Proteins, Transcription Factors, DNA-Cytosine Methylases, CpG Islands, DNA Methylation, Nuclear Receptor Co-Repressor 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
