{"day":"07","date_created":"2025-09-23T08:56:13Z","article_type":"original","date_published":"2025-08-07T00:00:00Z","type":"journal_article","issue":"15","_id":"20374","article_processing_charge":"Yes (in subscription journal)","doi":"10.1016/j.molcel.2025.06.027","OA_place":"publisher","publication_identifier":{"issn":["1097-2765"]},"file_date_updated":"2025-09-24T07:54:03Z","publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":85,"intvolume":" 85","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"publisher":"Elsevier","acknowledgement":"We thank M. Schütz for laboratory management, organization, and assistance with manuscript editing. We are grateful to all Thomä and Schübeler lab members. We thank Ulrich Hassiepen from Novartis for his support and insightful discussions on the kinetic analysis. This work was supported by funding from the European Research Council (ERC), under the European Union’s H2020 research program (NucEM, grant no. 884331); the Swiss National Science Foundation (SNF, grant no. 310030_301206 and 310030_214852); Krebsforschung (KFS, grant no. KFS-5933-08-2023); Novartis Research Foundation (to N.H.T.); the Novartis Freenovation (grant no. FN23-0000000514 to C.R.S.); the National Health and Medical Research Council CJ Martin Fellowship (APP1148380); the EU Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie grant (grant no. 748760); the South Australian immunoGENomics Cancer Institute grant funding from the Australian Government; and the Sylvia and Charles Viertel Charitable Foundation Senior Medical Research Fellowship (to L.I.).","status":"public","scopus_import":"1","language":[{"iso":"eng"}],"citation":{"ista":"Chakraborty D, Sandate CR, Isbel L, Kempf G, Weiss J, Cavadini S, Kater L, Seebacher J, Kozicka Z, Stoos L, Grand RS, Schübeler D, Michael AK, Thomä NH. 2025. Nucleosomes specify co-factor access to p53. Molecular Cell. 85(15), 2919–2936.e12.","ieee":"D. Chakraborty et al., “Nucleosomes specify co-factor access to p53,” Molecular Cell, vol. 85, no. 15. Elsevier, p. 2919–2936.e12, 2025.","short":"D. Chakraborty, C.R. Sandate, L. Isbel, G. Kempf, J. Weiss, S. Cavadini, L. Kater, J. Seebacher, Z. Kozicka, L. Stoos, R.S. Grand, D. Schübeler, A.K. Michael, N.H. Thomä, Molecular Cell 85 (2025) 2919–2936.e12.","ama":"Chakraborty D, Sandate CR, Isbel L, et al. Nucleosomes specify co-factor access to p53. Molecular Cell. 2025;85(15):2919-2936.e12. doi:10.1016/j.molcel.2025.06.027","mla":"Chakraborty, Deyasini, et al. “Nucleosomes Specify Co-Factor Access to P53.” Molecular Cell, vol. 85, no. 15, Elsevier, 2025, p. 2919–2936.e12, doi:10.1016/j.molcel.2025.06.027.","chicago":"Chakraborty, Deyasini, Colby R. Sandate, Luke Isbel, Georg Kempf, Joscha Weiss, Simone Cavadini, Lukas Kater, et al. “Nucleosomes Specify Co-Factor Access to P53.” Molecular Cell. Elsevier, 2025. https://doi.org/10.1016/j.molcel.2025.06.027.","apa":"Chakraborty, D., Sandate, C. R., Isbel, L., Kempf, G., Weiss, J., Cavadini, S., … Thomä, N. H. (2025). Nucleosomes specify co-factor access to p53. Molecular Cell. Elsevier. https://doi.org/10.1016/j.molcel.2025.06.027"},"ddc":["570"],"year":"2025","OA_type":"hybrid","has_accepted_license":"1","department":[{"_id":"AlMi"}],"month":"08","license":"https://creativecommons.org/licenses/by/4.0/","publication":"Molecular Cell","file":[{"file_name":"2025_MolecularCell_Chakraborty.pdf","content_type":"application/pdf","file_size":41813494,"date_updated":"2025-09-24T07:54:03Z","date_created":"2025-09-24T07:54:03Z","relation":"main_file","file_id":"20386","checksum":"e60390ca629b350af3221d4718ca6534","creator":"dernst","access_level":"open_access","success":1}],"page":"2919-2936.e12","date_updated":"2025-09-24T08:21:55Z","title":"Nucleosomes specify co-factor access to p53","PlanS_conform":"1","abstract":[{"lang":"eng","text":"Pioneer transcription factors (TFs) engage chromatinized DNA motifs. However, it is unclear how the resultant TF-nucleosome complexes are decoded by co-factors. In humans, the TF p53 regulates cell-cycle progression, apoptosis, and the DNA damage response, with a large fraction of p53-bound sites residing in nucleosome-harboring inaccessible chromatin. We examined the interaction of chromatin-bound p53 with co-factors belonging to the ubiquitin proteasome system (UPS). At two distinct motif locations on the nucleosome (super-helical location [SHL]−5.7 and SHL+5.9), the E3 ubiquitin ligase E6-E6AP was unable to bind nucleosome-engaged p53. The deubiquitinase USP7, on the other hand, readily engages nucleosome-bound p53 in vitro and in cells. A corresponding cryo-electron microscopy (cryo-EM) structure shows USP7 engaged with p53 and nucleosomes. Our work illustrates how chromatin imposes a co-factor-selective barrier for p53 interactors, whereby flexibly tethered interaction domains of co-factors and TFs govern compatibility between co-factors, TFs, and chromatin."}],"author":[{"full_name":"Chakraborty, Deyasini","last_name":"Chakraborty","first_name":"Deyasini"},{"first_name":"Colby R.","full_name":"Sandate, Colby R.","last_name":"Sandate"},{"first_name":"Luke","last_name":"Isbel","full_name":"Isbel, Luke"},{"full_name":"Kempf, Georg","last_name":"Kempf","first_name":"Georg"},{"first_name":"Joscha","full_name":"Weiss, Joscha","last_name":"Weiss"},{"last_name":"Cavadini","full_name":"Cavadini, Simone","first_name":"Simone"},{"first_name":"Lukas","last_name":"Kater","full_name":"Kater, Lukas"},{"first_name":"Jan","full_name":"Seebacher, Jan","last_name":"Seebacher"},{"first_name":"Zuzanna","last_name":"Kozicka","full_name":"Kozicka, Zuzanna"},{"first_name":"Lisa","full_name":"Stoos, Lisa","last_name":"Stoos"},{"last_name":"Grand","full_name":"Grand, Ralph S.","first_name":"Ralph S."},{"full_name":"Schübeler, Dirk","last_name":"Schübeler","first_name":"Dirk"},{"last_name":"Michael","id":"6437c950-2a03-11ee-914d-d6476dd7b75c","orcid":"0000-0002-6080-839X","full_name":"Michael, Alicia","first_name":"Alicia"},{"last_name":"Thomä","full_name":"Thomä, Nicolas H.","first_name":"Nicolas H."}],"quality_controlled":"1","oa_version":"Published Version","oa":1}