Targeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras
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Abstract
Many diseases, including cancer, stem from aberrant activation or overexpression of oncoproteins that are associated with multiple signaling pathways. Although proteins with catalytic activity can be successfully drugged, the majority of other protein families, such as transcription factors, remain intractable due to their lack of ligandable sites. In this study, we report the development of TRAnscription Factor TArgeting Chimeras (TRAFTACs) as a generalizable strategy for targeted transcription factor degradation. We show that TRAFTACs, which consist of a chimeric oligonucleotide that simultaneously binds to the transcription factor of interest (TOI) and to HaloTag-fused dCas9 protein, can induce degradation of the former via the proteasomal pathway. Application of TRAFTACs to two oncogenic TOIs, NF-κB and brachyury, suggests that TRAFTACs can be successfully employed for the targeted degradation of other DNA-binding proteins. Thus, TRAFTAC technology is potentially a generalizable strategy to induce degradation of other transcription factors both in vitro and in vivo.
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The TRAFTAC system has been used to degrade NF-κB and brachyury (TBXT) in human cell lines in a UPS-dependent manner that was specific to the dsDNA sequence and E3 ligase.
“The TRAFTAC system has been used to degrade NF-κB and brachyury (T-box transcription factor T; TBXT) in human cell lines in a UPS-dependent manner that was specific to the dsDNA sequence and E3 ligase43.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [43]
TRAFTACs consist of a HaloPROTAC that bridges an E3 ligase and a dCas9-HT7 fusion protein, then binds a bifunctional dsDNA-CRISPR-RNA to form a transcription factor-recruiting complex.
“TRAFTACs consist of a HaloPROTAC that bridges an E3 ligase and a dCas9–HT7 fusion protein, then binds a bifunctional dsDNA–CRISPR-RNA to form a transcription factor-recruiting complex.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [43]
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Cites
Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression
Qi, L. S., Larson, M. H., Gilbert, L. A., Doudna, J. A., Weissman, J. S., Arkin, A. P., & Lim, W. A. (2013) · Cell · doi:10.1016/j.cell.2013.02.022 · Cited by 5,016 · see citing works
Sakamoto, K. M., Kim, K. B., Kumagai, A., Mercurio, F., Crews, C. M., & Deshaies, R. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141230798 · Cited by 2,609 · see citing works
Self-citationCrystal structure of Cas9 in complex with guide RNA and target DNA
Nishimasu, H., Ran, F. A., Hsu, P. D., Konermann, S., Shehata, S. I., Dohmae, N., Ishitani, R., Zhang, F., & Nureki, O. (2014) · Cell · doi:10.1016/j.cell.2014.02.001 · Cited by 2,306 · see citing works
Phthalimide conjugation as a strategy for in vivo target protein degradation
Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760 · see citing works
Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer
Watson, P. A., Arora, V. K., & Sawyers, C. L. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4016 · Cited by 1,536 · see citing works
Induced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486 · see citing works
Self-citationThe IKK NF-κB system: a treasure trove for drug development
Karin, M., Yamamoto, Y., & Wang, Q. M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1279 · Cited by 1,364 · see citing works
Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases
Cho, S. W., Kim, S., Kim, Y., Kweon, J., Kim, H. S., Bae, S., & Kim, J.-S. (2014) · Genome Research · doi:10.1101/gr.162339.113 · Cited by 1,356 · see citing works
Regulation of NF-κB by TNF family cytokines
Hayden, M. S., & Ghosh, S. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.05.004 · Cited by 1,116 · see citing works
PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer
Raina, K., Lu, J., Qian, Y., Altieri, M., Gordon, D., Rossi, A. M. K., Wang, J., Chen, X., Dong, H., Siu, K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521738113 · Cited by 852 · see citing works
Self-citationA Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo
Bai, L., Zhou, H., Xu, R., Zhao, Y., Chinnaswamy, K., McEachern, D., Chen, J., Yang, C.-Y., Liu, Z., Wang, M., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.002 · Cited by 652 · see citing works
PROTACs: great opportunities for academia and industry
Sun, X., Gao, H., Yang, Y., He, M., Wu, Y., Song, Y.-G., Tong, Y., & Rao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0101-6 · Cited by 651 · see citing works
Drug discovery in the ubiquitin–proteasome system
Nalepa, G., Rolfe, M., & Harper, J. W. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2056 · Cited by 619 · see citing works
Modular PROTAC design for the degradation of oncogenic BCR-ABL
Lai, A. C., Toure, M., Hellerschmied, D., Salami, J., Jaime‐Figueroa, S., Ko, E., Hines, J., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507634 · Cited by 618 · see citing works
Self-citationCrystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA
Chen, F. E., Huang, D.-B., Chen, Y., & Ghosh, G. (1998) · Nature · doi:10.1038/34956 · Cited by 612 · see citing works
Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase
Smith, B. E., Wang, S. L., Jaime-Figueroa, S., Harbin, A., Wang, J., Hamman, B. D., & Crews, C. M. (2019) · Nature Communications · doi:10.1038/s41467-018-08027-7 · Cited by 517 · see citing works
Self-citationInduction of muscle pioneers and floor plate is distinguished by the zebrafish no tail mutation
Halpern, M. E., Ho, R. K., Walker, C., & Kimmel, C. B. (1993) · Cell · doi:10.1016/s0092-8674(05)80087-x · Cited by 508 · see citing works
HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins
Buckley, D. L., Raina, K., Darricarrere, N., Hines, J., Gustafson, J. L., Smith, I. E., Miah, A. H., Harling, J. D., & Crews, C. M. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00442 · Cited by 488 · see citing works
Self-citationElectrophilic PROTACs that degrade nuclear proteins by engaging DCAF16
Zhang, X., Crowley, V. M., Wucherpfennig, T. G., Dix, M. M., & Cravatt, B. F. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0279-5 · Cited by 487 · see citing works
Role of the NFκB-signaling pathway in cancer
Xia, L., Tan, S., Zhou, Y., Lin, J., Wang, H., Oyang, L., Tian, Y., Liu, L., Su, M., Wang, H., et al. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s161109 · Cited by 461 · see citing works
Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action
Osborne, C. K., Wakeling, A., & Nicholson, R. I. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601629 · Cited by 414 · see citing works
Buhimschi, A. D., Armstrong, H. A., Toure, M., Jaime-Figueroa, S., Chen, T. L., Lehman, A. M., Woyach, J. A., Johnson, A. J., Byrd, J. C., & Crews, C. M. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00391 · Cited by 394 · see citing works
Self-citationVerdine, G. L., & Walensky, L. D. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-2184 · Cited by 362 · see citing works
Salami, J., Alabi, S., Willard, R. R., Vitale, N. J., Wang, J., Dong, H., Jin, M., McDonnell, D. P., Crew, A. P., Neklesa, T. K., et al. (2018) · Communications Biology · doi:10.1038/s42003-018-0105-8 · Cited by 349 · see citing works
Self-citationExpression pattern of the Brachyury gene in whole-mount T WIS/T WIS mutant embryos
Herrmann, B. G. (1991) · Development · doi:10.1242/dev.113.3.913 · Cited by 348 · see citing works
Crystallographic structure of the T domain–DNA complex of the Brachyury transcription factor
Müller, C. W., & Herrmann, B. G. (1997) · Nature · doi:10.1038/39929 · Cited by 326 · see citing works
Sen, M., Thomas, S. M., Kim, S., Yeh, J. I., Ferris, R. L., Johnson, J. T., Duvvuri, U., Lee, J., Sahu, N., Joyce, S., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0191 · Cited by 313 · see citing works
Rice, M. A., Malhotra, S. V., & Stoyanova, T. I. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00801 · Cited by 311 · see citing works
T (brachyury) gene duplication confers major susceptibility to familial chordoma
Yang, X. R., Ng, D., Alcorta, D. A., et al. (2009) · Nature Genetics · doi:10.1038/ng.454 · Cited by 307 · see citing works
Hu, J., Hu, B., Wang, M., Xu, F., Miao, B., Yang, C., Wang, M., Liu, Z., Hayes, D. F., Chinnaswamy, K., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01572 · Cited by 286 · see citing works
Phosphatidylinositol 3-Kinase in Interleukin 1 Signaling
Reddy, S. A. G., Huang, J. H., & Liao, W. S. ‐. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.46.29167 · Cited by 230 · see citing works
Drugging Undruggable Molecular Cancer Targets
Lazo, J. S., & Sharlow, E. R. (2015) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103440 · Cited by 225 · see citing works
The T gene is necessary for normal mesodermal morphogenetic cell movements during gastrulation
Wilson, V. A., Manson, L., Skarnes, W. C., & Beddington, R. S. P. (1995) · Development · doi:10.1242/dev.121.3.877 · Cited by 216 · see citing works
Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation
Burslem, G. M., Schultz, A. R., Bondeson, D. P., Eide, C. A., Savage Stevens, S. L., Druker, B. J., & Crews, C. M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-1236 · Cited by 212 · see citing works
Self-citationPresneau, N., Shalaby, A. A., Ye, H., et al. (2010) · The Journal of Pathology · doi:10.1002/path.2816 · Cited by 201 · see citing works
Mutations affecting development of the notochord in zebrafish
Stemple, D. L., Solnica‐Krezel, L., Zwartkruis, F. J. T., Neuhauss, S. C. F., Schier, A. F., Malicki, J. J., Stainier, D. Y. R., Abdelilah, S., Rangini, Z., Mountcastle-Shah, E., et al. (1996) · Development · doi:10.1242/dev.123.1.117 · Cited by 198 · see citing works
Molecular mechanisms and mode of tamoxifen resistance in breast cancer
Ali, S. Y., Rasool, M., Chaoudhry, H., Pushparaj, P. N., Jha, P., Hafiz, A., Mahfooz, M., Sami, G. A., Kamal, M. A., Bashir, S., et al. (2016) · Bioinformation · doi:10.6026/97320630012135 · Cited by 190 · see citing works
Mellits, K. H., Hay, R. T., & Goodbourn, S. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.22.5059 · Cited by 182 · see citing works
Burslem, G. M., Song, J., Chen, X., Hines, J., & Crews, C. M. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b10320 · Cited by 176 · see citing works
Self-citationOrian, A., Gonen, H., Bercovich, B., Fajerman, I., Eytan, E., Israël, A., Mercurio, F., Iwaï, K., Schwartz, A. L., & Ciechanover, A. J. (2000) · The EMBO Journal · doi:10.1093/emboj/19.11.2580 · Cited by 174 · see citing works
Small-molecule targeting of brachyury transcription factor addiction in chordoma
Sharifnia, T., Wawer, M. J., Chen, T., Huang, Q., Weir, B. A., Sizemore, A. E., Lawlor, M. A., Goodale, A. B., Cowley, G. S., Vázquez, F., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0312-3 · Cited by 164 · see citing works
van Rooijen, E., Voest, E. E., Logister, I., Korving, J., Schwerte, T., Schulte‐Merker, S., Giles, R. H., & van Eeden, F. J. (2009) · Blood · doi:10.1182/blood-2008-07-167890 · Cited by 142 · see citing works
A common single-nucleotide variant in T is strongly associated with chordoma
Pillay, N., Plagnol, V., Tarpey, P. S., et al. (2012) · Nature Genetics · doi:10.1038/ng.2419 · Cited by 134 · see citing works
Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos
Tu, Z., Yang, W., Yan, S., Yin, A., Gao, J., Liu, X., Zheng, Y., Zheng, J., Li, Z., Yang, S., et al. (2017) · Scientific Reports · doi:10.1038/srep42081 · Cited by 133 · see citing works
Stabilization of the Max Homodimer with a Small Molecule Attenuates Myc-Driven Transcription
Struntz, N. B., Chen, A., Deutzmann, A., Wilson, R. M., Stefan, E., Evans, H. L., Ramirez, M. A., Liang, T., Caballero, F., Wildschut, M. H. E., et al. (2019) · Cell Chemical Biology · doi:10.1016/j.chembiol.2019.02.009 · Cited by 130 · see citing works
Zhang, H., Zhao, H., Xi, X.-X., Liu, Y., Xin, M., Mao, S., Zhang, J., Lu, A., & Zhang, S. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112061 · Cited by 129 · see citing works
Castell, A., Yan, Q., Fawkner, K., Hydbring, P., Zhang, F., Verschut, V., Franco, M., Zakaria, S. M., Bazzar, W., Goodwin, J., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-28107-4 · Cited by 126 · see citing works
Pande, V., & Ramos, M. J. (2005) · Current Medicinal Chemistry · doi:10.2174/0929867053363180 · Cited by 125 · see citing works
Antitumor activity of a pyrrole-imidazole polyamide
Yang, F., Nickols, N. G., Li, B. C., Marinov, G. K., SAID, J. W., & Dervan, P. B. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222035110 · Cited by 124 · see citing works
Precision Control of CRISPR-Cas9 Using Small Molecules and Light
Gangopadhyay, S. A., Cox, K. J., Manna, D., Lim, D., Maji, B., Zhou, Q., & Choudhary, A. (2019) · Biochemistry · doi:10.1021/acs.biochem.8b01202 · Cited by 117 · see citing works
A gene regulatory network directed by zebrafish No tail accounts for its roles in mesoderm formation
Morley, R. H., Lachani, K., Keefe, D., Gilchrist, M. J., Flicek, P., Smith, J. C., & Wardle, F. C. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808382106 · Cited by 111 · see citing works
Jaime-Figueroa, S., Buhimschi, A. D., Toure, M., Hines, J., & Crews, C. M. (2020) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.126877 · Cited by 88 · see citing works
Self-citationMolecular therapy to inhibit NFκB activation by transcription factor decoy oligonucleotides
Morishita, R., Tomita, N., Kaneda, Y., et al. (2004) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2003.10.008 · Cited by 87 · see citing works
Walhout, A. J. M., Gubbels, M., Bernards, R., van der Vliet, P. C., & Timmers, H. T. M. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.8.1493 · Cited by 83 · see citing works
Osthole inhibits triple negative breast cancer cells by suppressing STAT3
Dai, X.-X., Yin, C.-T., Zhang, Y., Guo, G., Zhao, C.-G., Wang, O.-C., Xiang, Y.-Q., Zhang, X.-H., & Liang, G. (2018) · Journal of experimental & clinical cancer research : CR · doi:10.1186/s13046-018-0992-z · Cited by 79 · see citing works
Targeted Disruption of Myc–Max Oncoprotein Complex by a Small Molecule
Choi, S. H., Mahankali, M., Lee, S. J., Hull, M. V., Petrassi, H. M., Chatterjee, A. K., Schultz, P. G., Jones, K. A., & Shen, W. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00799 · Cited by 75 · see citing works
Stabilizers of the Max Homodimer Identified in Virtual Ligand Screening Inhibit Myc Function
Jiang, H., Bower, K. E., Beuscher, A. E., Zhou, B., Bobkov, A. A., Olson, A. J., & Vogt, P. K. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.054858 · Cited by 62 · see citing works
The Roles of Embryonic Transcription Factor BRACHYURY in Tumorigenesis and Progression
Chen, M., Wu, Y., Zhang, H., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00961 · Cited by 57 · see citing works
Zhu, J., Kwan, K. M., & Mackem, S. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1601252113 · Cited by 56 · see citing works
Egashira, K., Suzuki, J., Ito, H., et al. (2008) · The Journal of Gene Medicine · doi:10.1002/jgm.1192 · Cited by 47 · see citing works
Inhibition of DNA Binding by NF-κB with Pyrrole-Imidazole Polyamides
Wurtz, N. R., Pomerantz, J. L., Baltimore, D., & Dervan, P. B. (2002) · Biochemistry · doi:10.1021/bi020114i · Cited by 40 · see citing works
Liu, C.-Y., Huang, T.-T., Chu, P.-Y., Huang, C.-T., Lee, C.-H., Wang, W.-L., Lau, K.-Y., Tsai, W.-C., Chao, T.-I., Su, J.-C., et al. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.114 · Cited by 40 · see citing works
Ganoderma lucidumextract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway
Rios-Fuller, T. J., Ortíz-Soto, G., Lacourt-Ventura, M., Maldonado-Martínez, G., Cubano, L. A., Schneider, R. J., & Martínez, M. (2018) · Oncotarget · doi:10.18632/oncotarget.26294 · Cited by 37 · see citing works
Imbaby, S., Matsuda, N., Tomita, K., Hattori, K., Palikhe, S., Yokoo, H., & Hattori, Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-72136-x · Cited by 37 · see citing works
Raffeiner, P., Röck, R., Schraffl, A., Hartl, M., Hart, J. R., Janda, K. D., Vogt, P. K., Stefan, E., & Bister, K. (2014) · Oncotarget · doi:10.18632/oncotarget.2588 · Cited by 31 · see citing works
Bt354 as a new STAT3 signaling pathway inhibitor against triple negative breast cancer
Chen, Y., Ji, M., Zhang, S., Xue, N., Xu, H., Lin, S., & Chen, X. (2018) · Journal of drug targeting · doi:10.1080/1061186x.2018.1452244 · Cited by 27 · see citing works
Oligonucleotides decoy to NF-kappaB: becoming a reality?
Stefano, D. D. (2011) · PubMed · Cited by 24 · see citing works
Establishment and genomic characterization of the new chordoma cell line Chor-IN-1
Bosotti, R., Magnaghi, P., Bella, S. D., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10044-3 · Cited by 15 · see citing works
Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor
Lee, D. S., O’Keefe, R. A., Ha, P. K., Grandis, J. R., & Johnson, D. E. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061608 · Cited by 11 · see citing works
A novel cold‐sensitive mutant of ntla reveals temporal roles of brachyury in zebrafish
Kimelman, D. (2016) · Developmental Dynamics · doi:10.1002/dvdy.24417 · Cited by 8 · see citing works
Abstract 4744: A prospective biospecimen collection study from patients with EGFR mutant tumors
Elkins, I. B., Feldman, J., Figueras, A., et al. (2019) · Experimental and Molecular Therapeutics · doi:10.1158/1538-7445.sabcs18-4744 · Cited by 7 · see citing works
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- Authors
- Samarasinghe, K. T. G., Jaime-Figueroa, S., Burgess, M., Nalawansha, D. A., Dai, K., Hu, Z., Bebenek, A., Holley, S. A., & Crews, C. M.
- Affiliations
- Yale University (US)
- Corresponding author
- Crews, Craig M.
- ORCID
- Venue
- Cell Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 28
- Issue
- 5
- Pages
- 648-661.e5
- ISSN
- 2451-9448 (ISSN-L)
- 2451-9456
- PMC
- PMC8524358
- OpenAlex
- W3144996175
- Cited by
- 182
- References
- 71
- Citations by year
- 2026: 26 · 2025: 35 · 2024: 35 · 2023: 37 · 2022: 33 · 2021: 15
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell chemical biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- transcription factor degradation, targeted protein degradation, chimeric oligonucleotides, dCas9, HaloTag, proteasomal degradation, NF-κB, Brachyury, oncoprotein, DNA-binding proteins
- MeSH terms
- Animals, Binding Sites, Cells, Cultured, DNA-Binding Proteins, Humans, Oligonucleotides, Transcription Factors, Zebrafish, HEK293 Cells
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