The KAP1 Corepressor Functions To Coordinate the Assembly of De Novo HP1-Demarcated Microenvironments of Heterochromatin Required for KRAB Zinc Finger Protein-Mediated Transcriptional Repression
Open accessAbstract
KAP1/TIF1beta is proposed to be a universal corepressor protein for the KRAB zinc finger protein (KRAB-zfp) superfamily of transcriptional repressors. To characterize the role of KAP1 and KAP1-interacting proteins in transcriptional repression, we investigated the regulation of stably integrated reporter transgenes by hormone-responsive KRAB and KAP1 repressor proteins. Here, we demonstrate that depletion of endogenous KAP1 levels by small interfering RNA (siRNA) significantly inhibited KRAB-mediated transcriptional repression of a chromatin template. Similarly, reduction in cellular levels of HP1alpha/beta/gamma and SETDB1 by siRNA attenuated KRAB-KAP1 repression. We also found that direct tethering of KAP1 to DNA was sufficient to repress transcription of an integrated transgene. This activity is absolutely dependent upon the interaction of KAP1 with HP1 and on an intact PHD finger and bromodomain of KAP1, suggesting that these domains function cooperatively in transcriptional corepression. The achievement of the repressed state by wild-type KAP1 involves decreased recruitment of RNA polymerase II, reduced levels of histone H3 K9 acetylation and H3K4 methylation, an increase in histone occupancy, enrichment of trimethyl histone H3K9, H3K36, and histone H4K20, and HP1 deposition at proximal regulatory sequences of the transgene. A KAP1 protein containing a mutation of the HP1 binding domain failed to induce any change in the histone modifications associated with DNA sequence…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
KAP1 has been reported to induce silencing of endogenous retroelements in part by coordinating the assembly of a HP1α-SETDB1 dependent co-repressor complex.
“KAP1 has been reported to induce silencing of endogenous retroelements31 in part by coordinating the assembly of a HP1α-SETDB1 dependent co-repressor complex32.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [32]
Cites
Structure and ligand of a histone acetyltransferase bromodomain
Dhalluin, C., Carlson, J. E., Zeng, L., He, C., Aggarwal, A. K., Zhou, M.-M., & Zhou, M.-M. (1999) · Nature · doi:10.1038/20974 · Cited by 1,732 · see citing works
Schultz, D. C., Ayyanathan, K., Negorev, D., Maul, G. G., & Rauscher, F. J. (2002) · Genes & Development · doi:10.1101/gad.973302 · Cited by 1,313 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Discovery and characterization of chromatin states for systematic annotation of the human genome
Ernst, J., & Kellis, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1662 · Cited by 1,033 · see citing works
“This specific combination has been independently reported as marking regions of KAP1 binding, a zinc-finger–specific co-repressor, which also shows a specific 44-fold enrichment for state 28 (refs”
BackgroundActivity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations
Fulco, C. P., Nasser, J., Jones, T. R., Munson, G., Bergman, D. T., Subramanian, V., Grossman, S. R., Anyoha, R., Doughty, B. R., Patwardhan, T. A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0538-0 · Cited by 1,111 · see citing works
Thakore, P. I., D'Ippolito, A. M., Song, L., Safi, A., Shivakumar, N. K., Kabadi, A. M., Reddy, T. E., Crawford, G. E., & Gersbach, C. A. (2015) · Nature Methods · doi:10.1038/nmeth.3630 · Cited by 1,012 · see citing works
“When localized to DNA, KRAB recruits a heterochromatin-forming complex that causes histone methylation and deacetylation 25–28 . dCas9-KRAB fusions have effectively silenced non-coding RNAs and single genes when targeted to promoter regions, 5’ untranslated regions, and proximal enhancer elements…”
KAP1 controls endogenous retroviruses in embryonic stem cells
Rowe, H. M., Jakobsson, J., Mesnard, D., Rougemont, J., Reynard, S., Aktas, T., Maillard, P. V., Layard-Liesching, H., Verp, S., Marquis, J., et al. (2010) · Nature · doi:10.1038/nature08674 · Cited by 874 · see citing works
Histones: annotating chromatin
Campos, E. I., & Reinberg, D. (2009) · Annual Review of Genetics · doi:10.1146/annurev.genet.032608.103928 · Cited by 852 · 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
“For the KAP1 ChIP we used an antibody recognizing the RBCC-domain of KAP1 (Sripathy et al., 2006) and HA ChIP were performed using anti-HA affinity matrix (Roche).”
MethodVan Meter, M., Kashyap, M., Rezazadeh, S., Geneva, A. J., Morello, T. D., Seluanov, A., & Gorbunova, V. (2014) · Nature Communications · doi:10.1038/ncomms6011 · Cited by 455 · see citing works
“KAP1 has been reported to induce silencing of endogenous retroelements 31 in part by coordinating the assembly of a HP1 α - SETDB1 dependent co-repressor complex 32 .”
Editing the epigenome: technologies for programmable transcription and epigenetic modulation
Thakore, P. I., Black, J. B., Hilton, I. B., & Gersbach, C. A. (2016) · Nature Methods · doi:10.1038/nmeth.3733 · Cited by 451 · see citing works
Ivanov, A. V., Peng, H., Yurchenko, V., Yap, K. L., Negorev, D. G., Schultz, D. C., Psulkowski, E., Fredericks, W. J., White, D. E., Maul, G. G., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.11.012 · Cited by 432 · see citing works
“Transient knockdown of SETDB1 in these conditions compromises repression and thus provides evidence for a functional link between KAP1 repression activity and SETDB1 recruitment (Sripathy et al., 2006).”
BackgroundInfluentialSelf-citationSilencing chromatin: comparing modes and mechanisms
Beisel, C., & Paro, R. (2011) · Nature reviews genetics · doi:10.1038/nrg2932 · Cited by 378 · see citing works
“Site-specific deposition of HP1, which is mediated by transcription factors, also establishes microenvironments of heterochromatin for the repression of gene transcriptio”
BackgroundGroner, A. C., Meylan, S., Ciuffi, A., Zangger, N., Ambrosini, G., Dénervaud, N., Bucher, P., & Trono, D. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000869 · Cited by 364 · see citing works
“nucleosome-remodeling and histone deacetylation (NuRD) complex, the nuclear receptor corepressor complex 1 (N-CoR1) and, at least during early embryonic development, de novo DNA methyltransferases [20–27].”
BackgroundEcco, G., Imbeault, M., & Trono, D. (2017) · Development · doi:10.1242/dev.132605 · Cited by 368 · see citing works
“, 2001), heterochromatin protein 1 (HP1) (Nielsen et al., 1999; Sripathy et al., 2006) and DNA methyltransferases (Quenneville et al.”
BackgroundInfluentialKAP1 Protein: An Enigmatic Master Regulator of the Genome
Iyengar, S., & Farnham, P. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.252569 · Cited by 367 · see citing works
TRIM28 mediates primer binding site-targeted silencing of murine leukemia virus in embryonic cells.
Wolf, D., & Goff, S. (2007) · Cell · doi:10.1016/j.cell.2007.07.026 · Cited by 366 · see citing works
Thompson, L. H. (2012) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2012.06.002 · Cited by 357 · see citing works
Adaptive Evolution in Zinc Finger Transcription Factors
Emerson, R., & Thomas, J. H. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000325 · Cited by 335 · see citing works
“SCAN, BTB, or SET domains [14–19,23–26].”
Fritsch, L., Robin, P., Mathieu, J. R. R., Souidi, M., Hinaux, H., Rougeulle, C., Harel-Bellan, A., Ameyar-Zazoua, M., & Ait-Si-Ali, S. (2010) · Molecular Cell · doi:10.1016/j.molcel.2009.12.017 · Cited by 321 · see citing works
“SETDB1 was indeed linked to gene silencing (Li et al., 2006; O’Geen et al., 2007; Regha et al., 2007; Sripathy et al., 2006; Takada et al., 2007; Wang et al., 2007) and to pericentric heterochromatin (Brower-Toland et al.”
BackgroundDynamic control of endogenous retroviruses during development
Rowe, H. M., & Trono, D. (2011) · Virology · doi:10.1016/j.virol.2010.12.007 · Cited by 278 · see citing works
Inactivation of a Human Kinetochore by Specific Targeting of Chromatin Modifiers
Nakano, M., Cardinale, S., Noskov, V., Gassmann, R., Vagnarelli, P., Kandels-Lewis, S., Larionov, V., Earnshaw, W., & Masumoto, H. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.02.001 · Cited by 267 · see citing works
“In a previous study, binding of a KAP-1 fusion protein to a targeted transgene reduced levels of histone H3K9 acetylation and H3K4 methylation, and increased H3K9me3 levels at the site (Sripathy et al., 2006).”
Herquel, B., Ouararhni, K., Khetchoumian, K., Ignat, M., Teletin, M., Mark, M., Béchade, G., van Dorsselaer, A., Sanglier-Cianférani, S., Hamiche, A., et al. (2011) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1101544108 · Cited by 225 · see citing works
The complexity of TRIM28 contribution to cancer
Czerwińska, P., Mazurek, S., & Wiznerowicz, M. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0374-4 · Cited by 272 · see citing works
“Together with KRAB-ZNF proteins, TRIM28 repress the expression of specific microRNA that target mitophagy-associated genes and therefore, sustain the proper mechanism of mitophagy during the erythropoiesis.”
BackgroundInfluentialCoevolution of retroelements and tandem zinc finger genesPreprint
Thomas, J. H., & Schneider, S. (2011) · Genome Research · doi:10.1101/gr.121749.111 · Cited by 218 · see citing works
“The lines show the linear least-squares best fit with its squared correlation coefficient R”
BackgroundTakahashi, K., Sugi, Y., Hosono, A., & Kaminogawa, S. (2009) · Journal of Immunology · doi:10.4049/jimmunol.0901271 · Cited by 190 · see citing works
Cys2His2 zinc finger protein family: Classification, functions, and major members
Razin, S., Borunova, V., Maksimenko, O., & Kantidze, O. (2012) · Biochemistry (Moscow) · doi:10.1134/s0006297912030017 · Cited by 186 · see citing works
Maksakova, I. A., Thompson, P. J., Goyal, P., Jones, S. J. M., Singh, P. B., Karimi, M. M., & Lorincz, M. C. (2013) · Epigenetics & Chromatin · doi:10.1186/1756-8935-6-15 · Cited by 185 · see citing works
“In addition, HP1 proteins directly interact with the PxVxL motif of KAP1 via their chromoshadow domain independent of H3K9 methylation state [29,40-42].”
BackgroundInfluentialZNF274 Recruits the Histone Methyltransferase SETDB1 to the 3′ Ends of ZNF Genes
Frietze, S. E., O’Geen, H., Blahnik, K. R., Jin, V. X., & Farnham, P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015082 · Cited by 166 · see citing works
“Most of the previous studies of KRAB domains have been performed by artificially tethering an isolated KRAB domain to the chromatin using transiently introduced or stably integrated artificial reporter constructs [37,38,39].”
BackgroundSUMO association with repressor complexes, emerging routes for transcriptional control.
García-Domínguez, M., & Reyes, J. (2009) · Biochimica et Biophysica Acta · doi:10.1016/j.bbagrm.2009.07.001 · Cited by 180 · see citing works
Genome-Wide Analysis of KAP1 Binding Suggests Autoregulation of KRAB-ZNFs
O'Geen, H., Squazzo, S. L., Iyengar, S., Blahnik, K., Rinn, J. L., Chang, H. Y., Green, R., & Farnham, P. J. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030089 · Cited by 178 · see citing works
“However, one study did show that an unspecified form of histone H3 methylated K9 is associated with RB1-mediated repression of a mammalian promoter [23] and other studies have shown association of binding of H3me3K9 with transcriptional repression of a promoter region after artificially tethering of a factor that can…”
BackgroundInfluentialTransposable elements in the mammalian germline: a comfortable niche or a deadly trap?
Zamudio, N., & Bourc’his, D. (2010) · Heredity · doi:10.1038/hdy.2010.53 · Cited by 179 · see citing works
“TRIM28 induces the heterochromatinization of this sequence by recruiting H3K9 di- and trimethylation, HP1 and the NuRD histone deacetylase complex (Sripathy et al., 2006).”
BackgroundLi, X., Lee, Y.-K., Jeng, J.-C., Yen, Y., Schultz, D. C., Shih, H.-M., & Ann, D. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706912200 · Cited by 168 · see citing works
Self-citationWolf, G., Yang, P., Füchtbauer, A., Füchtbauer, E., Silva, A. M., Park, C., Wu, W., Nielsen, A., Pedersen, F., & Macfarlan, T. (2015) · Genes & Development · doi:10.1101/gad.252767.114 · Cited by 168 · see citing works
“ZFP809 recruits the KRAB domainbinding corepressor KAP1 (TRIM28, TIF1b), which induces silencing via recruitment of histone deacetylases, heterochromatin protein 1 (HP1), and the histone methyltransferase SETDB1 (ESET, KMT1E) (Sripathy et al. 2006; Wolf and Goff 2007; Wolf et al. 2008).”
BackgroundRowe, H. M., Kapopoulou, A., Corsinotti, A., Fasching, L., Macfarlan, T. S., Tarabay, Y., Viville, S., Jakobsson, J., Pfaff, S. L., & Trono, D. (2012) · Genome Research · doi:10.1101/gr.147678.112 · Cited by 186 · see citing works
“…et al. 2007; Frietze et al. 2010), the NuRD (nucleosome remodeling and deacetylation) complex (Schultz et al. 2001), which contains the histone deacetylases HDAC1 and HDAC2 (for review, see McDonel et al. 2009), and heterochromatin protein 1 (HP-1) (Lechner et al. 2000; Sripathy et al. 2006).”
The function of Stat3 in tumor cells and their microenvironment.
Groner, B., Lucks, P., & Borghouts, C. (2008) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.06.005 · Cited by 165 · see citing works
TRIM28 SUMOylates and stabilizes NLRP3 to facilitate inflammasome activation
Qin, Y., Li, Q., Liang, W., Yan, R., Tong, L., Jia, M.-T., Zhao, C., & Zhao, W. (2021) · Nature Communications · doi:10.1038/s41467-021-25033-4 · Cited by 164 · see citing works
The impact of heterochromatin on DSB repair
Goodarzi, A. A., Noon, A. T., & Jeggo, P. A. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370569 · Cited by 149 · see citing works
Transposable elements in the mammalian embryo: pioneers surviving through stealth and service
Gerdes, P., Richardson, S. R., Mager, D. L., & Faulkner, G. J. (2016) · Genome biology · doi:10.1186/s13059-016-0965-5 · Cited by 163 · see citing works
“Moreover, some ERVs are marked by H3K9me3 and H4K20me3 for repression in ESCs but not in differentiated cells [6], suggesting that this pathway is used for de novo establishment of ds to mouse set silencing Trim28 [92] eterochromatin KRABZfps (likely) [93] en KRAB-Zfps me3 recruitment KRABZfps, Eset, NuRD deacetylase…”
BackgroundWhite, D., Rafalska-Metcalf, I. U., Ivanov, A. V., Corsinotti, A., Peng, H., Lee, S.-C., Trono, D., Janicki, S. M., & Rauscher, F. J. (2012) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-11-0134 · Cited by 152 · see citing works
“KAP1-Mut2 does not colocalize with HP1 at pericentric heterochromatin and shows reduced transcriptional repressor activity (18).”
White, D. E., Negorev, D., Peng, H.-Z., Ivanov, A., Maul, G., & Rauscher, F. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-4138 · Cited by 152 · see citing works
“KAP1 assembles these proteins onto KRAB-ZFPs to coordinate the deacetylation and methylation of histones, as well as the deposition of HP1, all of which cooperatively result in heritable gene silencing through the formation of heterochromatin (11).”
BackgroundRadzisheuskaya, A., Shlyueva, D., Müller, I., & Helin, K. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw583 · Cited by 145 · see citing works
TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells
Fasching, L., Kapopoulou, A., Sachdeva, R., Petri, R., Jönsson, M. E., Männe, C., Turelli, P., Jern, P., Cammas, F., Trono, D., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.12.004 · Cited by 138 · see citing works
“TRIM28 then induces repressive histone modifications by recruiting multiprotein complexes including the H3K9 methyltransferase SETDB1 (also known as ESET), the histone deacetylase-containing NuRD complex, and heterochromatin protein 1 (HP1) (Schultz et al., 2002; Sripathy et al., 2006).”
BackgroundKAP1-Mediated Epigenetic Repression in the Forebrain Modulates Behavioral Vulnerability to Stress
Jakobsson, J., Cordero, M. I., Bisaz, R., Groner, A. C., Busskamp, V., Bensadoun, J., Cammas, F. M., Losson, R., Mansuy, I. M., Sandi, C., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.036 · Cited by 130 · see citing works
“The human genome contains more than 400 genes coding for Krüppel-associated box (KRAB) zinc finger proteins (KRABZFPs) (Huntley et al., 2006; Sripathy et al., 2006; Urrutia, 2003), and comparative sequence analyses indicate that this family of epigenetic repressors is vertebrate specific.”
BackgroundInfluentialInterplay between Epigenetics and Genetics in Cancer
Choi, J. D., & Lee, J.-S. (2013) · Genomics & Informatics · doi:10.5808/gi.2013.11.4.164 · Cited by 131 · see citing works
In vivo gene regulation using tetracycline-regulatable systems
Stieger, K., Belbellaa, B., Guiner, C. L., Moullier, P., & Rolling, F. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2008.12.016 · Cited by 128 · see citing works
“basal transcription machinery [34] [35] [36] [37] [38] [39] [40] .”
Wiznerowicz, M., Jakobsson, J., Szulc, J., Liao, S., Quazzola, A., Beermann, F., Aebischer, P., & Trono, D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705898200 · Cited by 128 · see citing works
Functional Analysis of KAP1 Genomic Recruitment
Iyengar, S., Ivanov, A., Jin, V. X., Rauscher, F., & Farnham, P. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.01331-10 · Cited by 125 · see citing works
“How can our current results be reconciled with previous studies that suggest that KAP1 functions as a repressor of transcription? In previous work, KAP1 has been studied using artificial systems (1, 12, 27, 30).”
ResultThe TRIM family protein KAP1 inhibits HIV-1 integration.
Allouch, A., Primio, C. D., Alpi, E., Lusic, M., Arosio, D., Giacca, M., & Cereseto, A. (2011) · Cell Host and Microbe · doi:10.1016/j.chom.2011.05.004 · Cited by 122 · see citing works
“KAP1 mediates gene silencing (Ivanov et al., 2007; Sripathy et al., 2006) by recruiting on target promoters the NuRD histone deacetylase (HDAC) complex (Schultz et al.”
BackgroundJeevan-Raj, B., Robert, I., Heyer, V., Page, A., Wang, J. H., Cammas, F., Alt, F., Losson, R., & Reina-San-Martin, B. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20110118 · Cited by 116 · see citing works
“However, this is unlikely as the transcriptional repressor activity of KAP1 requires its association with HP1 (Sripathy et al., 2006), and we show that the expression of a KAP1 mutant protein that cannot associate with HP1 (Cammas et al.”
BackgroundDrosophila SETDB1 Is Required for Chromosome 4 Silencing
Seum, C., Reo, E., Peng, H.-Z., Rauscher, F., Spierer, P., & Bontron, S. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030076 · Cited by 114 · see citing works
“Mammalian SETDB1 is recruited to DNA together with HP1, either via the KRAB-zinc-finger protein KAP1 corepressor [27,45] or by the ERG transcription factor [46], or as a component of the MBD1-mAM/MCAF1-SETDB1 complex [30,47,48].”
BackgroundMossink, B., Negwer, M., Schubert, D., & Nadif Kasri, N. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03714-5 · Cited by 114 · see citing works
Epigenetic regulation of development by histone lysine methylation
Dambacher, S., Hahn, M., & Schotta, G. (2010) · Heredity · doi:10.1038/hdy.2010.49 · Cited by 108 · see citing works
“Setdb1 is an important functional constituent of the Kap1 corepressor complex that mainly uses H3K9me3 as a means of gene repression (Sripathy et al., 2006).”
BackgroundKRAB-zinc finger protein gene expansion in response to active retrotransposons in the murine lineage
Wolf, G., Iaco, A. D., Sun, M.-A., Bruno, M., Tinkham, M., Hoang, D., Mitra, A., Ralls, S., Trono, D., & Macfarlan, T. (2020) · eLife · doi:10.7554/elife.56337 · Cited by 107 · see citing works
Chen, L., Chen, D., Kurtyka, C. A., Rawal, B., Fulp, W. J., Haura, E. B., & Cress, W. D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.380865 · Cited by 108 · see citing works
SUMO‐modified Sp3 represses transcription by provoking local heterochromatic gene silencing
Stielow, B., Sapetschnig, A., Wink, C., Krüger, I., & Suske, G. (2008) · EMBO Reports · doi:10.1038/embor.2008.127 · Cited by 106 · see citing works
“HP1a, SETDB1 and SUV4-20H, as well as H3K9me3 and H4K20me3 modifications are present at the Dhfr promoter in wild-type MEFs but not in Sp3-deficient MEFs (Fig 5).”
BackgroundInfluentialCrichton, J. H., Dunican, D. S., MacLennan, M., Meehan, R., & Adams, I. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1468-0 · Cited by 104 · see citing works
Genomic Targets of the KRAB and SCAN Domain-containing Zinc Finger Protein 263*
Frietze, S., Lan, X., Jin, V. X., & Farnham, P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.063032 · Cited by 103 · see citing works
KAPtain in charge of multiple missions: Emerging roles of KAP1
Cheng, C.-T. (2014) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v5.i3.308 · Cited by 99 · see citing works
Genetic and epigenetic defects in mental retardation
Kramer, J. M., & van Bokhoven, H. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.08.009 · Cited by 87 · see citing works
Regulation of E2F1 Function by the Nuclear Corepressor KAP1*
Wang, C., Rauscher, F., Cress, W., & Chen, J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704757200 · Cited by 96 · see citing works
A somatic role for the histone methyltransferase Setdb1 in endogenous retrovirus silencing
Kato, M., Takemoto, K., & Shinkai, Y. (2018) · Nature Communications · doi:10.1038/s41467-018-04132-9 · Cited by 94 · see citing works
Human BAHD1 promotes heterochromatic gene silencing
Bierne, H., Tham, T. N., Batsché, E., Dumay, A., Guillou, M. L., Kernéis-Golsteyn, S., Regnault, B., Seeler, J., Muchardt, C., Feunteun, J., et al. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0901259106 · Cited by 93 · see citing works
Brower-Toland, B., Riddle, N. C., Jiang, H., Huisinga, K. L., & Elgin, S. C. R. (2009) · Genetics · doi:10.1534/genetics.108.100271 · Cited by 86 · see citing works
Retroviral Transcriptional Regulation and Embryonic Stem Cells: War and Peace
Schlesinger, S., & Goff, S. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.01293-14 · Cited by 86 · see citing works
“initiate the epigenetic marking of the provirus (15, 16).”
BackgroundHierarchical inactivation of a synthetic human kinetochore by a chromatin modifier.
Cardinale, S., Bergmann, J. H., Kelly, D. A., Nakano, M., Valdivia, M., Kimura, H., Masumoto, H., Larionov, V., & Earnshaw, W. C. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-06-0489 · Cited by 86 · see citing works
“…responsible for HAC kinetochore inactivation downstream of tTS binding, TetR:EYFP was fused to a KAP1 construct lacking the first 20 residues (KAP1 20 ; Figure 2A), which has been reported to function identically to the full-length protein in in vivo gene silencing assays (Sripathy et al., 2006).”
Chen, H., Zhang, S., Gao, X., Gao, X., Xu, X., LV, Y. J., Zhang, Y., Zhu, Z., Zhang, C., Li, Q., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.313262 · Cited by 92 · see citing works
A Unique SUMO-2-Interacting Motif within LANA Is Essential for KSHV Latency
Cai, Q., Cai, S., Zhu, C., Verma, S. C., Choi, J.-Y., & Robertson, E. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003750 · Cited by 81 · see citing works
“KAP1 itself cannot bind DNA directly and recruits or coordinates the assembly of several chromatin-remodeling proteins including the histone deacetylase complex (NCoR1) [56], and the heterochromatin protein 1 (HP1) family member [57].”
BackgroundActivation of endogenous retroviruses during brain development causes an inflammatory response
Jönsson, M. E., Garza, R., Sharma, Y., Petri, R., Södersten, E., Johansson, J. G., Johansson, P. A., Atacho, D. A., Pircs, K., Madsen, S., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2020106423 · Cited by 80 · see citing works
“Trim28 attracts a multiprotein complex that establishes transcriptional silencing and deposition of the repressive histone mark H3K9me3 (Sripathy et al , 2006).”
Sumoylation in Physiology, Pathology and Therapy
Şahin, U., de Thé, H., & Lallemand-Breitenbach, V. (2022) · Cells · doi:10.3390/cells11050814 · Cited by 92 · see citing works
Krischuns, T., Günl, F., Henschel, L., Binder, M., Willemsen, J., Schloer, S., Rescher, U., Gerlt, V., Zimmer, G., Nordhoff, C., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02229 · Cited by 78 · see citing works
Williams, R. M., Senanayake, U., Artibani, M., Taylor, G., Wells, D., Ahmed, A., & Sauka-Spengler, T. (2018) · Development · doi:10.1242/dev.160333 · Cited by 77 · see citing works
“6G), whereas the KRAB domain is thought to recruit a chromatin compaction complex thus rendering enhancers inaccessible (Sripathy et al., 2006) (Fig.”
BackgroundPRC1 marks the difference in plant PcG repression.
Calonje, M. (2014) · Molecular Plant · doi:10.1093/mp/sst150 · Cited by 77 · see citing works
KAP1/TRIM28: an inhibitor of IRF5 function in inflammatory macrophages.
Eames, H. L., Saliba, D. G., Krausgruber, T., Lanfrancotti, A., Ryzhakov, G., & Udalova, I. (2012) · Immunobiology · doi:10.1016/j.imbio.2012.07.026 · Cited by 77 · see citing works
Stoll, G., Oda, S., Chong, Z.-S., Yu, M.-M., McLaughlin, S., & Modis, Y. (2019) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1901318116 · Cited by 76 · see citing works
“Mutations in the HP1-binding motif of KAP1 (R487E/V488E) abolished its transcriptional activity, while disruption of the PHD (C651A) resulted in moderate derepression of the reporter, consistent with previous reports (16, 34).”
ResultHide and seek: how chromatin-based pathways silence retroelements in the mammalian germline
Molaro, A., & Malik, H. S. (2016) · Current Opinion in Genetics and Development · doi:10.1016/j.gde.2015.12.001 · Cited by 76 · see citing works
Measuring in vivo protein half-life.
Bojkowska, K., de Sio, F. R. S., Barde, I., Offner, S., Verp, S., Heinis, C., Johnsson, K., & Trono, D. (2011) · Chemistry and Biology · doi:10.1016/j.chembiol.2011.03.014 · Cited by 75
Peng, H.-Z., Ivanov, A., Oh, H., Lau, Y.-F. C., & Rauscher, F. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.032086 · Cited by 75 · see citing works
Yoon, J., Lee, K.-S., Park, J., Yu, K., Paik, S., & Kang, Y.-K. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002234 · Cited by 75 · see citing works
“Mammalian SETDB1/ESET is known to associate with several transcriptional regulators such as the ERG protein [39], mAM [38], KRAB-zinc-finger protein KAP1 [30,31], and MBD1/MCAF1 [48,49,50].”
BackgroundTranscription Factor Effector Domains
Frietze, S. E., & Farnham, P. (2011) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-90-481-9069-0_12 · Cited by 82 · see citing works
“tein 1 (HP1) isoforms, histone deacetylases, and SETDB1, a SET-domain histone methyltransferase that methylates histone H3 at lysine 9 [23, 114, 115].”
BackgroundCitrate boosts the performance of phosphopeptide analysis by UPLC-ESI-MS/MS.
Winter, D., Seidler, J., Ziv, Y., Shiloh, Y., & Lehmann, W. (2009) · Journal of Proteome Research · doi:10.1021/pr800304n · Cited by 75 · 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
“Stable KAP1 knockdown cell lines K928-cI10 (HEK293) and U2OS-K4 (U2OS) were kindly provided by David Schultz [18,19].”
BackgroundMethodInfluentialHonda, S., Lewis, Z. A., Shimada, K., Fischle, W., Sack, R., & Selker, E. (2012) · Nature Structural &Molecular Biology · doi:10.1038/nsmb.2274 · Cited by 72 · see citing works
Primer Binding Site-Dependent Restriction of Murine Leukemia Virus Requires HP1 Binding by TRIM28
Wolf, D., Cammas, F., Losson, R., & Goff, S. (2008) · Journal of Virology · doi:10.1128/jvi.02445-07 · Cited by 72 · see citing works
Li, G.-Y., Zhu, Y.-F., Shao, D., Chang, H., Zhang, X., Zhou, D., Gao, Y.-Q., Lan, K., & Deng, Q. (2018) · Hepatology · doi:10.1002/hep.29406 · Cited by 71 · see citing works
“transferable module with DNA binding–dependent transcriptional repression activity.((23,24)) The KRABCre fusion protein induced rcccDNA with an efficiency similar to wt Cre (Fig.”
SUMO, a small, but powerful, regulator of double-strand break repair
Garvin, A. J., & Morris, J. R. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0281 · Cited by 73 · see citing works
Proviral Silencing in Embryonic Cells is Regulated by Yin Yang 1
Schlesinger, S., Lee, A., Wang, G. Z., Green, L., & Goff, S. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.003 · Cited by 68 · see citing works
“These include the histoneH3K9methyltransferasesESET (Matsui et al., 2010) andG9a (Leung et al., 2011) and the heterochromatin-associated protein HP1 (Sripathy et al., 2006), involved in the heterochromatinization and repression of class I and II ERVs and some exogenous retroviruses: the Polycomb group (PcG) I and II p…”
Emerging role of SETDB1 as a therapeutic target
Karanth, A. V., Maniswami, R. R., Prashanth, S., Govindaraj, H., Padmavathy, R., Jegatheesan, S. K., Mullangi, R., & Rajagopal, S. (2017) · Expert opinion on therapeutic targets · doi:10.1080/14728222.2017.1279604 · Cited by 67 · see citing works
“This subsequently leads to the binding of KRAB-zfp to KAP1 by its 75 amino acid KRAB box to form a KRAB–KAP1 repression complex [44].”
BackgroundMascle, X., Germain-Desprez, D., Huynh, P., Estephan, P., & Aubry, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611429200 · Cited by 67 · see citing works
Grimmer, M., Stolzenburg, S., Ford, E., Lister, R., Blancafort, P., & Farnham, P. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku708 · Cited by 66 · see citing works
Quénet, D., Gasser, V., Fouillen, L., Cammas, F., Sanglier-Cianférani, S., Losson, R., & Dantzer, F. (2008) · The FASEB Journal · doi:10.1096/fj.08-113464 · Cited by 64 · see citing works
Chang, C., Chou, H.-Y. E., Lin, Y.-S., Huang, K.-H., Chang, C.-J., Hsu, T.-C., & Lee, S.-C. (2008) · BMC Molecular Biology · doi:10.1186/1471-2199-9-61 · Cited by 64 · see citing works
“A TIF1β-containing multiprotein complex regulates various protein activities or genes [19].”
BackgroundKAP1/TRIM28: Transcriptional Activator and/or Repressor of Viral and Cellular Programs?
Randolph, K., Hyder, U., & D'Orso, I. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.834636 · Cited by 63 · see citing works
“The RBCC domain is followed by a ~200 amino acid intrinsically disordered region (IDR) (Figures 2A, B) that contains an internal PxVxL motif involved in HP1-binding for gene repression (Ryan et al., 1999; Sripathy et al., 2006), and a C-terminal tandem plant homologybromodomain (PHD-BD) cassette involved in intramolec…”
BackgroundHutchins, A., & Pei, D. (2015) · Science Bulletin · doi:10.1007/s11434-015-0905-x · Cited by 63 · see citing works
Epigenome engineering: new technologies for precision medicine
Sgro, A., & Blancafort, P. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa1000 · Cited by 96 · see citing works
“The repressor domain most commonly fused to DBDs is the Krüppel-associated box KRAB (82).”
BackgroundTRIM28 as a novel transcriptional elongation factor
Bunch, H., & Calderwood, S. K. (2015) · BMC Molecular Biology · doi:10.1186/s12867-015-0040-x · Cited by 60 · see citing works
“TRIM28 and transcriptional elongation TRIM28 has been shown to be a powerful gene repressor when overexpressed in cells [31, 49].”
BackgroundZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains
Shi, H., Strogantsev, R., Takahashi, N., Kazachenka, A., Lorincz, M., Hemberger, M., & Ferguson-Smith, A. (2019) · Epigenetics & Chromatin · doi:10.1186/s13072-019-0295-4 · Cited by 60 · see citing works
“Members of the co-repressor complex include the DNA methyltransferases, histone methyltransferase SETDB1 (also known as ESET), heterochromatin protein 1 (HP1), the histone demethylase LSD1, and NuRD histone deacetylase complex [9, 10].”
BackgroundLi, X., Lin, H. H., Chen, H., Xu, X., Shih, H.-M., & Ann, D. K. (2010) · Science Signaling · doi:10.1126/scisignal.2000781 · Cited by 59 · see citing works
Gou, Z., Liu, R.-R., Zhao, G.-P., Zheng, M., Li, P., Wang, H., Zhu, Y., Chen, J.-L., & Wen, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033627 · Cited by 59 · see citing works
“The mechanism involves recruiting KRAB-associated protein 1 (KAP1), triggering de novo DNA methylation [32], and the forming of a multimolecular complex comprising histone deacetylases, which induces transcriptional repression through the formation of heterochromatin [33,34,35].”
BackgroundJiang, W.-Q., Zhong, Z.-H., Nguyen, A., Henson, J. D., Toouli, C., Braithwaite, A., & Reddel, R. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200810084 · Cited by 58 · see citing works
“, 2004) and 5-GAGGAGCACAATACTTGGGAA-3 (Sripathy et al., 2006).”
Kauzlaric, A., Ecco, G., Cassano, M., Duc, J., Imbeault, M., & Trono, D. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173746 · Cited by 55 · see citing works
KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair
Lin, Y.-H., Yuan, J., Pei, H., Liu, T., Ann, D. K., & Lou, Z. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123935 · Cited by 56 · see citing works
Histone H3 lysine methylation in cognition and intellectual disability disordersPreprint
Parkel, S., López‐Atalaya, J. P., & Barco, Á. (2013) · Learning & Memory · doi:10.1101/lm.029363.112 · Cited by 59 · see citing works
“These TFs contain a transcriptional repression domain KRAB (Krüppel-associated box) and thereby can bind the corepressor KRAB-associated protein 1 (KAP1) which, in turn, may recruit the H3K9 KMT SETD1B to the locus (Sripathy et al. 2006).”
Background
- Authors
- Sripathy, S. P., Stevens, J., & Schultz, D. C.
- Affiliations
- Case Comprehensive Cancer Center (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2006-11-01
- Volume
- 26
- Issue
- 22
- Pages
- 8623-8638
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1636786
- OpenAlex
- W2105073128
- Cited by
- 323
- References
- 70
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 20 · 2023: 15 · 2022: 14 · 2021: 21 · 2020: 24 · 2019: 14 · 2018: 14 · 2017: 14 · 2016: 15 · 2015: 19 · 2014: 13 · 2013: 12 · 2012: 20
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Case Comprehensive Cancer Center, Case Western Reserve University
- National Cancer Institute (K01CA099093, CA-99093)
- 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 › Chromatin Remodeling and Cancer
- Keywords
- KRAB zinc finger proteins, transcriptional repression, heterochromatin, HP1 proteins, SETDB1, PHD finger, bromodomain, histone modifications, H3K9 trimethylation, H3K4 methylation, nuclear compartmentalization, chromatin templates, RNA polymerase II recruitment
- MeSH terms
- Tripartite Motif-Containing Protein 28, Chromobox Protein Homolog 5, Cell Line, Chromatin, DNA-Binding Proteins, Heterochromatin, Histones, Hormones, Humans, Histone-Lysine N-Methyltransferase, Protein Methyltransferases, Repressor Proteins, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Transfection, Genes, Reporter, Integrases, Saccharomyces cerevisiae Proteins, RNA, Small Interfering
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
