Identification of a transcriptional repressor related to the noncatalytic domain of histone deacetylases 4 and 5
Open accessAbstract
Histone deacetylases (HDACs) are involved in regulating transcription by modifying the core histones of the nucleosome. To date, six HDACs have been identified in mammalian cells: the yeast RPD3 homologs HDAC1, 2, and 3 and the yeast HDA1 homologs HDAC4, 5, and 6. HDAC4 and HDAC5 contain a noncatalytic N-terminal domain. Herein, we report the identification of a protein HDRP ( HD AC- r elated p rotein) that shares 50% identity in deduced amino acid sequence to the noncatalytic N-terminal domain of HDAC4 and 5. The steady-state levels of HDRP mRNA are high in human brain, heart, and skeletal muscle and low in the several other tissues. HDRP has an apparent molecular mass of approximately 75 kDa. HDRP does not possess intrinsic HDAC activity but forms complexes with both HDAC1 and HDAC3. HDRP represses both basal and activated transcription in transient transfection assays when tethered to DNA as a Gal4-fusion protein. HDAC inhibitors do not reverse transcriptional repression mediated by Gal4–HDRP. Thus, HDRP is a transcriptional repressor and can repress transcription in the presence of HDAC inhibitors.
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A natural HDAC9 splice variant lacking the HDAC domain (MITR/HDRP) and analogous artificially truncated forms of other class IIa members retain full transcriptional repressive functions.
“A natural HDAC9 splice variant lacking the HDAC domain [myocyte enhancer factor-2 interacting transcription repressor/HDAC-related protein (MITR/HDRP)] as well as analogous artificially truncated forms of other class IIa members retain full transcriptional repressive functions (16,17).”
From Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases (2007) · cites this paper as [16]
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Cites
Histone acetylation in chromatin structure and transcription
Grunstein, M. (1997) · Nature · doi:10.1038/38664 · Cited by 2,884 · see citing works
A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p
Taunton, J., Hassig, C. A., & Schreiber, S. L. (1996) · Science · doi:10.1126/science.272.5260.408 · Cited by 1,829 · see citing works
How eukaryotic transcriptional activators work
Ptashne, M. (1988) · Nature · doi:10.1038/335683a0 · Cited by 1,828 · see citing works
Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors
Finnin, M. S., Donigian, J. R., Cohen, A., Richon, V. M., Rifkind, R. A., Marks, P. A., Breslow, R., & Pavletich, N. P. (1999) · Nature · doi:10.1038/43710 · Cited by 1,714 · see citing works
Self-citationTranscriptional activation: A complex puzzle with few easy pieces
Tjian, R., & Maniatis, T. (1994) · Cell · doi:10.1016/0092-8674(94)90227-5 · Cited by 1,108 · see citing works
A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases
Richon, V. M., Emiliani, S., Verdin, E., Webb, Y., Breslow, R., Rifkind, R. A., & Marks, P. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.3003 · Cited by 914 · see citing works
Self-citationCooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins
Molkentin, J. D., Black, B. L., Martin, J. F., & Olson, E. N. (1995) · Cell · doi:10.1016/0092-8674(95)90139-6 · Cited by 819 · see citing works
Three proteins define a class of human histone deacetylases related to yeast Hda1p
Grozinger, C. M., Hassig, C. A., & Schreiber, S. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.9.4868 · Cited by 770 · see citing works
Rundlett, S. E., Carmen, A. A., Kobayashi, R., Bavykin, S. G., Turner, B. M., & Grunstein, M. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14503 · Cited by 618 · see citing works
HDAC4 deacetylase associates with and represses the MEF2 transcription factor
Miska, E. A., Karlsson, C., Langley, E., Nielsen, S. J., Pines, J., & Kouzarides, T. (1999) · The EMBO Journal · doi:10.1093/emboj/18.18.5099 · Cited by 551 · see citing works
Yang, W., Inouye, C. J., Zeng, Y., Bearss, D. J., & Seto, E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.12845 · Cited by 542 · see citing works
Yang, W., Yao, Y., Sun, J.-M., Davie, J., & Seto, E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.44.28001 · Cited by 433 · see citing works
Active repression mechanisms of eukaryotic transcription repressors
Hanna‐Rose, W., & Hansen, U. M. (1996) · Trends in Genetics · doi:10.1016/0168-9525(96)10022-6 · Cited by 311 · see citing works
HDAC4, a Human Histone Deacetylase Related to Yeast HDA1, Is a Transcriptional Corepressor
Wang, A. H., Bertos, N. R., Vezmar, M., Pelletier, N., Crosato, M., Heng, H. H., Th’ng, J., Han, J., & Yang, X.-J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.11.7816 · Cited by 294 · see citing works
Characterization of a human RPD3 ortholog, HDAC3
Emiliani, S., Fischle, W., Lint, C. M. V., Al-Abed, Y., & Verdin, E. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.2795 · Cited by 292 · see citing works
Jin, S. V., & Scotto, K. W. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.4377 · Cited by 289 · see citing works
Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo
Kadosh, D., & Struhl, K. (1998) · Genes & Development · doi:10.1101/gad.12.6.797 · Cited by 234 · see citing works
Activation of the Myogenic Lineage by MEF2A, a Factor that Induces and Cooperates with MyoD
Kaushal, S., Schneider, J. W., Nadal‐Ginard, B., & Mahdavi, V. (1994) · Science · doi:10.1126/science.7973707 · Cited by 230 · see citing works
Johnson, A. D. (1995) · Cell · doi:10.1016/0092-8674(95)90524-3 · Cited by 228 · see citing works
Identification of a New Family of Higher Eukaryotic Histone Deacetylases
Verdel, A., & Khochbin, S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.4.2440 · Cited by 227 · see citing works
A New Family of Human Histone Deacetylases Related toSaccharomyces cerevisiae HDA1p
Fischle, W., Emiliani, S., Hendzel, M. J., Nagase, T., Nomura, N., Voelter, W., & Verdin, E. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.17.11713 · Cited by 225 · see citing works
MEF‐2 function is modified by a novel co‐repressor, MITR
Sparrow, D. B., Miska, E. A., Langley, E., Reynaud‐Deonauth, S., Kotecha, S., Towers, N., Spohr, G., Kouzarides, T., & Mohun, T. J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.18.5085 · Cited by 196 · see citing works
HDA1 and HDA3 Are Components of a Yeast Histone Deacetylase (HDA) Complex
Carmen, A. A., Rundlett, S. E., & Grunstein, M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.26.15837 · Cited by 188 · see citing works
Dangond, F., Hafler, D. A., Tong, J. K., Randall, J., Kojima, R., Utku, N., & Gullans, S. R. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.8033 · Cited by 108 · see citing works
Localization of a gene for non-syndromic hearing loss (DFNA5) to chromosome 7p15
Camp, G. V., Coucke, P. J., Balemans, W., et al. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.11.2159 · Cited by 101 · see citing works
New eukaryotic transcriptional repressers
Saha, S., Brickman, J. M., Lehming, N., et al. (1993) · Nature · doi:10.1038/363648a0 · Cited by 86 · see citing works
Knutsen, T., Mickley, L. A., Ried, T., Green, E. D., du Manoir, S., Schröck, E., Macville, M. V. E., Ning, Y., Robey, R. W., Polymeropoulos, M. H., et al. (1998) · Genes Chromosomes and Cancer · doi:10.1002/(sici)1098-2264(199809)23:1 · Cited by 75 · see citing works
Black, B. L., Ligon, K. L., Zhang, Y., & Olson, E. N. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.43.26659 · Cited by 75 · see citing works
Mao, Z., & Nadal‐Ginard, B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.24.14371 · Cited by 43 · see citing works
Loss of heterozygosity at 11q23.1 and survival in breast cancer: Results of a large European study
Laake, K., Launonen, V., Niederacher, D., Gudlaugsdottir, S., Seitz, S., Rio, P. G., Champ�me, M.-H., Bièche, I., Birnbaum, D., White, G. R. M., et al. (1999) · Genes Chromosomes and Cancer · doi:10.1002/(sici)1098-2264(199907)25:3 · Cited by 38 · see citing works
Webb, Y., Zhou, X., Ngo, L., Cornish, V. W., Stahl, J., Erdjument‐Bromage, H., Tempst, P., Rifkind, R. A., Marks, P. A., Breslow, R., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.20.14280 · Cited by 36 · see citing works
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Research works printed but not linked: 1
- [22]Schmidt H, Wurl P, Taubert H, Meye A, Bache M, Holzhausen H J, Hinze R. Genes Chromosomes Cancer. 1999;25:205–211. [PubMed] [Google Scholar]
Cited by
Sorted by citations
Histone deacetylases (HDACs): characterization of the classical HDAC family
RUIJTER, A. J. M. D., GENNIP, A. H. V., CARON, H. N., KEMP, S., & KUILENBURG, A. B. P. V. (2003) · Biochemical Journal · doi:10.1042/bj20021321 · Cited by 3,114 · see citing works
Fischle, W., Dequiedt, F., Hendzel, M. J., Guenther, M. G., Lazar, M. A., Voelter, W., & Verdin, E. (2002) · Molecular Cell · doi:10.1016/s1097-2765(01)00429-4 · Cited by 754 · see citing works
Chemical phylogenetics of histone deacetylases
Bradner, J. E., West, N., Grachan, M. L., Greenberg, E. F., Haggarty, S. J., Warnow, T., & Mazitschek, R. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.313 · Cited by 720 · see citing works
Class II histone deacetylases: versatile regulators
Verdin, E., Dequiedt, F., & Kasler, H. G. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(03)00073-8 · Cited by 664 · see citing works
Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases
Lahm, A., Paolini, C., Pallaoro, M., Nardi, M. C., Jones, P., Neddermann, P., Sambucini, S., Bottomley, M. J., Lo Surdo, P., Carfı́, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706487104 · Cited by 566 · see citing works
Human HDAC7 Histone Deacetylase Activity Is Associated with HDAC3in Vivo
Fischle, W., Dequiedt, F., Fillion, M., Hendzel, M. J., Voelter, W., & Verdin, E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104935200 · Cited by 232 · see citing works
Durst, K. L., Lutterbach, B., Kummalue, T., Friedman, A. D., & Hiebert, S. W. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.2.607-619.2003 · Cited by 161 · see citing works
Neuroprotection by histone deacetylase-related protein
Morrison, B. E., Majdzadeh, N., Zhang, X., Lyles, A., Bassel-Duby, R., Olson, E. N., & D'Mello, S. R. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.9.3550-3564.2006 · Cited by 100 · see citing works
Schlumm, F., Mauceri, D., Freitag, H. E., & Bading, H. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.432773 · Cited by 76 · see citing works
- Authors
- Zhou, X., Richon, V. M., Rifkind, R. A., & Marks, P. A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Marks, Paul A.
- ORCID
- Zhou, Xianbo
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-02
- Volume
- 97
- Issue
- 3
- Pages
- 1056-1061
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC15519
- OpenAlex
- W2007996284
- Cited by
- 120
- References
- 31
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 6 · 2021: 3 · 2020: 8 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center
- Foundation for Promotion of Cancer Research
- National Cancer Institute (CA-0974823)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- 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
- Keywords
- transcriptional repressor, histone deacetylase, HDAC4, HDAC5, transcriptional repression, HDAC1, HDAC3, protein-protein complex formation, histone deacetylase inhibitors, tissue-specific gene expression, GAL4 fusion proteins
- MeSH terms
- Histone Deacetylase 3, Amino Acid Sequence, Animals, Chlorocebus aethiops, Histone Deacetylases, Humans, Molecular Sequence Data, Organ Specificity, Recombinant Fusion Proteins, Repressor Proteins, RNA, Messenger, Transcription, Genetic, Transfection, Sequence Alignment, Sequence Homology, Amino Acid, COS Cells, Histone Deacetylase 1
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