{"entity": "researcher", "timestamp": "2026-09-28T11:51:18.711Z", "family": "Colicchia", "given": "Valeria", "initials": "V", "orcid": "0000-0001-5290-5379", "affiliations": ["Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/be63770eda8c4ac6845d7a43742f6c78.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/be63770eda8c4ac6845d7a43742f6c78"}}, "publications": [{"entity": "publication", "iuid": "31a55d1f431f4e3a856ca9634904e168", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/31a55d1f431f4e3a856ca9634904e168.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/31a55d1f431f4e3a856ca9634904e168"}}, "title": "New regulators of the tetracycline-inducible gene expression system identified by chemical and genetic screens.", "authors": [{"family": "Colicchia", "given": "Valeria", "initials": "V", "orcid": "0000-0001-5290-5379", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be63770eda8c4ac6845d7a43742f6c78.json"}}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Sirozh", "given": "Oleksandra", "initials": "O"}, {"family": "Porebski", "given": "Bartlomiej", "initials": "B"}, {"family": "Balan", "given": "Mirela", "initials": "M"}, {"family": "Li", "given": "Xuexin", "initials": "X", "orcid": "0000-0001-5824-9720", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8668449288f0444b93f8473a3407f186.json"}}, {"family": "Lidemalm", "given": "Louise", "initials": "L"}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J"}, {"family": "H\u00fchn", "given": "Daniela", "initials": "D"}, {"family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab1f07900e6e466d83763e5fe0020ed6.json"}}], "type": "journal article", "published": "2022-10-00", "journal": {"title": "FEBS Open Bio", "issn": "2211-5463", "volume": "12", "issue": "10", "pages": "1896-1908", "issn-l": "2211-5463"}, "abstract": "The tetracycline repressor (tetR)-regulated system is a widely used tool to specifically control gene expression in mammalian cells. Based on this system, we generated a human osteosarcoma cell line, which allows for the inducible expression of an EGFP fusion of the TAR DNA-binding protein 43 (TDP-43), which has been linked to neurodegenerative diseases. Consistent with previous findings, TDP-43 overexpression led to the accumulation of aggregates and limited the viability of U2OS. Using this inducible system, we conducted a chemical screen with a library that included FDA-approved drugs. While the primary screen identified several compounds that prevented TDP-43 toxicity, further experiments revealed that these chemicals abrogated the doxycycline-dependent TDP-43 expression. This antagonistic effect was observed with both doxycycline and tetracycline, and in several Tet-On cell lines expressing different genes, confirming the general effect of these compounds as inhibitors of the tetR system. Using the same cell line, a genome-wide CRISPR/Cas9 screen identified epigenetic regulators such as the G9a methyltransferase and TRIM28 as potential modifiers of TDP-43 toxicity. Yet again, further experiments revealed that G9a inhibition or TRIM28 loss prevented doxycycline-dependent expression of TDP-43. In summary, we have identified new chemical and genetic regulators of the tetR system, thereby raising awareness of the limitations of this approach to conduct chemical or genetic screening in mammalian cells.", "doi": "10.1002/2211-5463.13482", "pmid": "36062323", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9527584"}], "notes": [], "created": "2026-09-23T13:09:45.648Z", "modified": "2026-09-23T13:09:45.742Z"}]}