--- _id: '12156' abstract: - lang: eng text: Models of transcriptional regulation that assume equilibrium binding of transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than in bacteria. This could be due to the non-equilibrium nature of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium mechanisms is vast and predominantly uninteresting. The key question is therefore how this space can be navigated efficiently, to focus on mechanisms and models that are biologically relevant. In this review, we advocate for the normative role of theory—theory that prescribes rather than just describes—in providing such a focus. Theory should expand its remit beyond inferring mechanistic models from data, towards identifying non-equilibrium gene regulatory schemes that may have been evolutionarily selected, despite their energy consumption, because they are precise, reliable, fast, or otherwise outperform regulation at equilibrium. We illustrate our reasoning by toy examples for which we provide simulation code. acknowledgement: 'This work was supported through the Center for the Physics of Biological Function (PHYe1734030) and by National Institutes of Health Grants R01GM097275 and U01DK127429 (TG). GT acknowledges the support of the Austrian Science Fund grant FWF P28844 and the Human Frontiers Science Program. ' article_number: '100435' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Benjamin full_name: Zoller, Benjamin last_name: Zoller - first_name: Thomas full_name: Gregor, Thomas last_name: Gregor - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: '1' citation: ama: Zoller B, Gregor T, Tkačik G. Eukaryotic gene regulation at equilibrium, or non? Current Opinion in Systems Biology. 2022;31(9). doi:10.1016/j.coisb.2022.100435 apa: Zoller, B., Gregor, T., & Tkačik, G. (2022). Eukaryotic gene regulation at equilibrium, or non? Current Opinion in Systems Biology. Elsevier. https://doi.org/10.1016/j.coisb.2022.100435 chicago: Zoller, Benjamin, Thomas Gregor, and Gašper Tkačik. “Eukaryotic Gene Regulation at Equilibrium, or Non?” Current Opinion in Systems Biology. Elsevier, 2022. https://doi.org/10.1016/j.coisb.2022.100435. ieee: B. Zoller, T. Gregor, and G. Tkačik, “Eukaryotic gene regulation at equilibrium, or non?,” Current Opinion in Systems Biology, vol. 31, no. 9. Elsevier, 2022. ista: Zoller B, Gregor T, Tkačik G. 2022. Eukaryotic gene regulation at equilibrium, or non? Current Opinion in Systems Biology. 31(9), 100435. mla: Zoller, Benjamin, et al. “Eukaryotic Gene Regulation at Equilibrium, or Non?” Current Opinion in Systems Biology, vol. 31, no. 9, 100435, Elsevier, 2022, doi:10.1016/j.coisb.2022.100435. short: B. Zoller, T. Gregor, G. Tkačik, Current Opinion in Systems Biology 31 (2022). date_created: 2023-01-12T12:08:51Z date_published: 2022-09-01T00:00:00Z date_updated: 2023-02-13T09:20:34Z day: '01' ddc: - '570' department: - _id: GaTk doi: 10.1016/j.coisb.2022.100435 file: - access_level: open_access checksum: 97ef01e0cc60cdc84f45640a0f248fb0 content_type: application/pdf creator: dernst date_created: 2023-01-24T12:14:10Z date_updated: 2023-01-24T12:14:10Z file_id: '12362' file_name: 2022_CurrentBiology_Zoller.pdf file_size: 2214944 relation: main_file success: 1 file_date_updated: 2023-01-24T12:14:10Z has_accepted_license: '1' intvolume: ' 31' issue: '9' keyword: - Applied Mathematics - Computer Science Applications - Drug Discovery - General Biochemistry - Genetics and Molecular Biology - Modeling and Simulation language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '09' oa: 1 oa_version: Published Version project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: Current Opinion in Systems Biology publication_identifier: issn: - 2452-3100 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Eukaryotic gene regulation at equilibrium, or non? tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 31 year: '2022' ... --- _id: '9018' abstract: - lang: eng text: Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy. article_processing_charge: No article_type: original author: - first_name: May M full_name: Bakail, May M id: FB3C3F8E-522F-11EA-B186-22963DDC885E last_name: Bakail orcid: 0000-0002-9592-1587 - first_name: Albane full_name: Gaubert, Albane last_name: Gaubert - first_name: Jessica full_name: Andreani, Jessica last_name: Andreani - first_name: Gwenaëlle full_name: Moal, Gwenaëlle last_name: Moal - first_name: Guillaume full_name: Pinna, Guillaume last_name: Pinna - first_name: Ekaterina full_name: Boyarchuk, Ekaterina last_name: Boyarchuk - first_name: Marie-Cécile full_name: Gaillard, Marie-Cécile last_name: Gaillard - first_name: Regis full_name: Courbeyrette, Regis last_name: Courbeyrette - first_name: Carl full_name: Mann, Carl last_name: Mann - first_name: Jean-Yves full_name: Thuret, Jean-Yves last_name: Thuret - first_name: Bérengère full_name: Guichard, Bérengère last_name: Guichard - first_name: Brice full_name: Murciano, Brice last_name: Murciano - first_name: Nicolas full_name: Richet, Nicolas last_name: Richet - first_name: Adeline full_name: Poitou, Adeline last_name: Poitou - first_name: Claire full_name: Frederic, Claire last_name: Frederic - first_name: Marie-Hélène full_name: Le Du, Marie-Hélène last_name: Le Du - first_name: Morgane full_name: Agez, Morgane last_name: Agez - first_name: Caroline full_name: Roelants, Caroline last_name: Roelants - first_name: Zachary A. full_name: Gurard-Levin, Zachary A. last_name: Gurard-Levin - first_name: Geneviève full_name: Almouzni, Geneviève last_name: Almouzni - first_name: Nadia full_name: Cherradi, Nadia last_name: Cherradi - first_name: Raphael full_name: Guerois, Raphael last_name: Guerois - first_name: Françoise full_name: Ochsenbein, Françoise last_name: Ochsenbein citation: ama: Bakail MM, Gaubert A, Andreani J, et al. Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. 2019;26(11):1573-1585.e10. doi:10.1016/j.chembiol.2019.09.002 apa: Bakail, M. M., Gaubert, A., Andreani, J., Moal, G., Pinna, G., Boyarchuk, E., … Ochsenbein, F. (2019). Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. Elsevier. https://doi.org/10.1016/j.chembiol.2019.09.002 chicago: Bakail, May M, Albane Gaubert, Jessica Andreani, Gwenaëlle Moal, Guillaume Pinna, Ekaterina Boyarchuk, Marie-Cécile Gaillard, et al. “Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.” Cell Chemical Biology. Elsevier, 2019. https://doi.org/10.1016/j.chembiol.2019.09.002. ieee: M. M. Bakail et al., “Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1,” Cell Chemical Biology, vol. 26, no. 11. Elsevier, p. 1573–1585.e10, 2019. ista: Bakail MM, Gaubert A, Andreani J, Moal G, Pinna G, Boyarchuk E, Gaillard M-C, Courbeyrette R, Mann C, Thuret J-Y, Guichard B, Murciano B, Richet N, Poitou A, Frederic C, Le Du M-H, Agez M, Roelants C, Gurard-Levin ZA, Almouzni G, Cherradi N, Guerois R, Ochsenbein F. 2019. Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. 26(11), 1573–1585.e10. mla: Bakail, May M., et al. “Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.” Cell Chemical Biology, vol. 26, no. 11, Elsevier, 2019, p. 1573–1585.e10, doi:10.1016/j.chembiol.2019.09.002. short: M.M. Bakail, A. Gaubert, J. Andreani, G. Moal, G. Pinna, E. Boyarchuk, M.-C. Gaillard, R. Courbeyrette, C. Mann, J.-Y. Thuret, B. Guichard, B. Murciano, N. Richet, A. Poitou, C. Frederic, M.-H. Le Du, M. Agez, C. Roelants, Z.A. Gurard-Levin, G. Almouzni, N. Cherradi, R. Guerois, F. Ochsenbein, Cell Chemical Biology 26 (2019) 1573–1585.e10. date_created: 2021-01-19T11:04:50Z date_published: 2019-11-21T00:00:00Z date_updated: 2023-02-23T13:46:53Z day: '21' doi: 10.1016/j.chembiol.2019.09.002 extern: '1' external_id: pmid: - '31543461' intvolume: ' 26' issue: '11' keyword: - Clinical Biochemistry - Molecular Medicine - Biochemistry - Molecular Biology - Pharmacology - Drug Discovery language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.chembiol.2019.09.002 month: '11' oa: 1 oa_version: Published Version page: 1573-1585.e10 pmid: 1 publication: Cell Chemical Biology publication_identifier: issn: - 2451-9456 publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1 type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 26 year: '2019' ... --- _id: '13436' abstract: - lang: eng text: Cross-metathesis reactions of α,β-unsaturated sulfones and sulfoxides in the presence of molybdenum and ruthenium pre-catalysts were tested. A selective metahesis reaction was achieved between functionalized terminal olefins and vinyl sulfones by using the ‘second generation’ ruthenium catalysts 1c–h while the highly active Schrock catalyst 1b was found to be functional group incompatible with vinyl sulfones. The cross-metathesis products were isolated in good yields with an excellent (E)-selectivity. Both the molybdenum and ruthenium-based complexes were, however, incompatible with α,β- and β,γ-unsaturated sulfoxides. article_processing_charge: No article_type: original author: - first_name: Anna full_name: Michrowska, Anna last_name: Michrowska - first_name: Michał full_name: Bieniek, Michał last_name: Bieniek - first_name: Mikhail full_name: Kim, Mikhail last_name: Kim - first_name: Rafal full_name: Klajn, Rafal id: 8e84690e-1e48-11ed-a02b-a1e6fb8bb53b last_name: Klajn - first_name: Karol full_name: Grela, Karol last_name: Grela citation: ama: Michrowska A, Bieniek M, Kim M, Klajn R, Grela K. Cross-metathesis reaction of vinyl sulfones and sulfoxides. Tetrahedron. 2003;59(25):4525-4531. doi:10.1016/s0040-4020(03)00682-3 apa: Michrowska, A., Bieniek, M., Kim, M., Klajn, R., & Grela, K. (2003). Cross-metathesis reaction of vinyl sulfones and sulfoxides. Tetrahedron. Elsevier. https://doi.org/10.1016/s0040-4020(03)00682-3 chicago: Michrowska, Anna, Michał Bieniek, Mikhail Kim, Rafal Klajn, and Karol Grela. “Cross-Metathesis Reaction of Vinyl Sulfones and Sulfoxides.” Tetrahedron. Elsevier, 2003. https://doi.org/10.1016/s0040-4020(03)00682-3. ieee: A. Michrowska, M. Bieniek, M. Kim, R. Klajn, and K. Grela, “Cross-metathesis reaction of vinyl sulfones and sulfoxides,” Tetrahedron, vol. 59, no. 25. Elsevier, pp. 4525–4531, 2003. ista: Michrowska A, Bieniek M, Kim M, Klajn R, Grela K. 2003. Cross-metathesis reaction of vinyl sulfones and sulfoxides. Tetrahedron. 59(25), 4525–4531. mla: Michrowska, Anna, et al. “Cross-Metathesis Reaction of Vinyl Sulfones and Sulfoxides.” Tetrahedron, vol. 59, no. 25, Elsevier, 2003, pp. 4525–31, doi:10.1016/s0040-4020(03)00682-3. short: A. Michrowska, M. Bieniek, M. Kim, R. Klajn, K. Grela, Tetrahedron 59 (2003) 4525–4531. date_created: 2023-08-01T10:39:34Z date_published: 2003-06-16T00:00:00Z date_updated: 2023-08-08T12:44:17Z day: '16' doi: 10.1016/s0040-4020(03)00682-3 extern: '1' intvolume: ' 59' issue: '25' keyword: - Organic Chemistry - Drug Discovery - Biochemistry language: - iso: eng month: '06' oa_version: None page: 4525-4531 publication: Tetrahedron publication_identifier: eissn: - 1464-5416 issn: - 0040-4020 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Cross-metathesis reaction of vinyl sulfones and sulfoxides type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 59 year: '2003' ...