Academic Journal
Ki67 deficiency impedes chromatin accessibility and BCR gene rearrangement
| العنوان: | Ki67 deficiency impedes chromatin accessibility and BCR gene rearrangement |
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| المؤلفون: | Ding, Zhoujie, Hagan, Maree, Yan, Feng, Schroer, Nick W.Y., Polmear, Jack, Good-Jacobson, Kim L., Dvorscek, Alexandra R., Pitt, Catherine, O’Donnell, Kristy, Nutt, Stephen L., Zotos, Dimitra, McKenzie, Craig, Hill, Danika L., Robinson, Marcus J., Quast, Isaak, Koentgen, Frank, Tarlinton, David M. |
| المساهمون: | MASSIVE, Nectar, Swedish Research Council, Monash University, National Health and Medical Research Council, Cancer Council Victoria, Swiss National Science Foundation |
| المصدر: | Journal of Experimental Medicine ; volume 221, issue 8 ; ISSN 0022-1007 1540-9538 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2024 |
| الوصف: | The proliferation marker Ki67 has been attributed critical functions in maintaining mitotic chromosome morphology and heterochromatin organization during the cell cycle, indicating a potential role in developmental processes requiring rigid cell-cycle control. Here, we discovered that despite normal fecundity and organogenesis, germline deficiency in Ki67 resulted in substantial defects specifically in peripheral B and T lymphocytes. This was not due to impaired cell proliferation but rather to early lymphopoiesis at specific stages where antigen–receptor gene rearrangements occurred. We identified that Ki67 was required for normal global chromatin accessibility involving regulatory regions of genes critical for checkpoint stages in B cell lymphopoiesis. In line with this, mRNA expression of Rag1 was diminished and gene rearrangement was less efficient in the absence of Ki67. Transgenes encoding productively rearranged immunoglobulin heavy and light chains complemented Ki67 deficiency, completely rescuing early B cell development. Collectively, these results identify a unique contribution from Ki67 to somatic antigen–receptor gene rearrangement during lymphopoiesis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1084/jem.20232160 |
| DOI: | 10.1084/jem.20232160/1928981/jem_20232160.pdf |
| الاتاحة: | http://dx.doi.org/10.1084/jem.20232160 https://rupress.org/jem/article-pdf/doi/10.1084/jem.20232160/1928981/jem_20232160.pdf |
| Rights: | http://www.rupress.org/terms/ ; https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| رقم الانضمام: | edsbas.C5C4786B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1084/jem.20232160 |
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