{"extern":"1","type":"journal_article","external_id":{"pmid":["37386214"]},"abstract":[{"text":"The genomic binding sites of the transcription factor (TF) and tumor suppressor p53 are unusually diverse with regard to their chromatin features, including histone modifications, raising the possibility that the local chromatin environment can contextualize p53 regulation. Here, we show that epigenetic characteristics of closed chromatin, such as DNA methylation, do not influence the binding of p53 across the genome. Instead, the ability of p53 to open chromatin and activate its target genes is locally restricted by its cofactor Trim24. Trim24 binds to both p53 and unmethylated histone 3 lysine 4 (H3K4), thereby preferentially localizing to those p53 sites that reside in closed chromatin, whereas it is deterred from accessible chromatin by H3K4 methylation. The presence of Trim24 increases cell viability upon stress and enables p53 to affect gene expression as a function of the local chromatin state. These findings link H3K4 methylation to p53 function and illustrate how specificity in chromatin can be achieved, not by TF-intrinsic sensitivity to histone modifications, but by employing chromatin-sensitive cofactors that locally modulate TF function.","lang":"eng"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41594-023-01021-8"}],"doi":"10.1038/s41594-023-01021-8","publication":"Nature Structural & Molecular Biology","date_created":"2024-03-21T07:53:24Z","pmid":1,"month":"06","publication_identifier":{"eissn":["1545-9985"],"issn":["1545-9993"]},"year":"2023","date_published":"2023-06-29T00:00:00Z","citation":{"ista":"Isbel L, Iskar M, Durdu S, Weiss J, Grand RS, Hietter-Pfeiffer E, Kozicka Z, Michael AK, Burger L, Thomä NH, Schübeler D. 2023. Readout of histone methylation by Trim24 locally restricts chromatin opening by p53. Nature Structural &#38; Molecular Biology. 30(7), 948–957.","ama":"Isbel L, Iskar M, Durdu S, et al. Readout of histone methylation by Trim24 locally restricts chromatin opening by p53. <i>Nature Structural &#38; Molecular Biology</i>. 2023;30(7):948-957. doi:<a href=\"https://doi.org/10.1038/s41594-023-01021-8\">10.1038/s41594-023-01021-8</a>","mla":"Isbel, Luke, et al. “Readout of Histone Methylation by Trim24 Locally Restricts Chromatin Opening by P53.” <i>Nature Structural &#38; Molecular Biology</i>, vol. 30, no. 7, Springer Nature, 2023, pp. 948–57, doi:<a href=\"https://doi.org/10.1038/s41594-023-01021-8\">10.1038/s41594-023-01021-8</a>.","apa":"Isbel, L., Iskar, M., Durdu, S., Weiss, J., Grand, R. S., Hietter-Pfeiffer, E., … Schübeler, D. (2023). Readout of histone methylation by Trim24 locally restricts chromatin opening by p53. <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-023-01021-8\">https://doi.org/10.1038/s41594-023-01021-8</a>","chicago":"Isbel, Luke, Murat Iskar, Sevi Durdu, Joscha Weiss, Ralph S. Grand, Eric Hietter-Pfeiffer, Zuzanna Kozicka, et al. “Readout of Histone Methylation by Trim24 Locally Restricts Chromatin Opening by P53.” <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41594-023-01021-8\">https://doi.org/10.1038/s41594-023-01021-8</a>.","short":"L. Isbel, M. Iskar, S. Durdu, J. Weiss, R.S. Grand, E. Hietter-Pfeiffer, Z. Kozicka, A.K. Michael, L. Burger, N.H. Thomä, D. Schübeler, Nature Structural &#38; Molecular Biology 30 (2023) 948–957.","ieee":"L. Isbel <i>et al.</i>, “Readout of histone methylation by Trim24 locally restricts chromatin opening by p53,” <i>Nature Structural &#38; Molecular Biology</i>, vol. 30, no. 7. Springer Nature, pp. 948–957, 2023."},"publication_status":"published","keyword":["Molecular Biology","Structural Biology"],"article_type":"original","language":[{"iso":"eng"}],"page":"948-957","intvolume":"        30","date_updated":"2024-03-25T12:37:20Z","title":"Readout of histone methylation by Trim24 locally restricts chromatin opening by p53","publisher":"Springer Nature","oa":1,"status":"public","oa_version":"Published Version","volume":30,"scopus_import":"1","quality_controlled":"1","article_processing_charge":"No","author":[{"last_name":"Isbel","first_name":"Luke","full_name":"Isbel, Luke"},{"last_name":"Iskar","first_name":"Murat","full_name":"Iskar, Murat"},{"first_name":"Sevi","last_name":"Durdu","full_name":"Durdu, Sevi"},{"last_name":"Weiss","first_name":"Joscha","full_name":"Weiss, Joscha"},{"first_name":"Ralph S.","last_name":"Grand","full_name":"Grand, Ralph S."},{"full_name":"Hietter-Pfeiffer, Eric","last_name":"Hietter-Pfeiffer","first_name":"Eric"},{"first_name":"Zuzanna","last_name":"Kozicka","full_name":"Kozicka, Zuzanna"},{"full_name":"Michael, Alicia","orcid":"0000-0002-6080-839X","first_name":"Alicia","last_name":"Michael","id":"6437c950-2a03-11ee-914d-d6476dd7b75c"},{"first_name":"Lukas","last_name":"Burger","full_name":"Burger, Lukas"},{"full_name":"Thomä, Nicolas H.","first_name":"Nicolas H.","last_name":"Thomä"},{"first_name":"Dirk","last_name":"Schübeler","full_name":"Schübeler, Dirk"}],"day":"29","issue":"7","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"15149"}