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CSR occurs between highly repetitive switch sequences located upstream of constant gene exons, and is initiated by the Activation-Induced cytidine Deaminase\n                    <jats:italic>via<\/jats:italic>\n                    transcription-dependent deamination of single-stranded DNA targets at switch regions. CSR is preceded by germline transcription and is controlled by the super-enhancer 3\u2032 regulatory region (3\u2032RR) in an activation-specific manner. The 3\u2019RR is composed of four enhancers (hs3a, hs1-2, hs3b, and hs4) which act in synergy, and its long-range activity correlates with the enhancers\u2019 transcription. In addition to its function as a tumor suppressor, the p53 transcription factor controls various developmental and cellular processes. This multifaceted function is largely due to its context-dependent transcriptional activity, involving both activation and repression of a myriad of target genes. Despite its potential importance for CSR, which implies multiple layers of transcriptional, epigenetic and DNA break\/repair regulations, the role of p53 in CSR is still unclear. Here, by using a mouse line devoid of p53, we show that p53 regulates CSR in an isotype-specific manner. Moreover, we provide evidence that p53 has a dual role in the control of germline transcription as it acts both as an activator and a repressor. Finally, we show that p53 is required for hs4 transcription, suggesting a role for p53 in the regulation of the 3\u2019RR\u2019s transcriptional activity.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-49435-w","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T02:15:59Z","timestamp":1777083359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential regulation of immunoglobulin class switch recombination by the tumor suppressor p53"],"prefix":"10.1038","volume":"16","author":[{"given":"Kawtar","family":"Hanefioui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Dauba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Payrault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadila","family":"Guessous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Amine","family":"Khamlichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,25]]},"reference":[{"key":"49435_CR1","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1146\/annurev.immunol.23.021704.115830","volume":"24","author":"D Jung","year":"2006","unstructured":"Jung, D., Giallourakis, C., Mostoslavsky, R. & Alt, F. 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