Ki67 deficiency impedes chromatin accessibility and BCR gene rearrangement

• DOI: 10.1084/jem.20232160
• Publication Date: 2024-06-06T13:53:49Z
• Authors: Zhoujie Ding; Maree Hagan; Feng Yan; Nick W.Y. Schroer; Jack Polmear; Kim L. Good-Jacobson; Alexandra R. Dvor...; Catherine Pitt; Kristy O’Donnell; Stephen L. Nutt; Dimitra Zotos; Craig McKenzie; Danika L. Hill; Marcus J. Robinson; Isaak Quast; Frank Koentgen; David M. Tarlinton
• Keywords: Lymphopoiesis; Gene rearrangement

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 developmental processes requiring rigid cell-cycle control. Here, we discovered that despite normal fecundity organogenesis, germline deficiency resulted substantial defects specifically peripheral B T lymphocytes. This was not due to impaired but rather early lymphopoiesis at specific stages where antigen–receptor gene rearrangements occurred. We identified required for global chromatin accessibility involving regulatory regions of genes checkpoint lymphopoiesis. In line with this, mRNA expression Rag1 diminished rearrangement less efficient absence Ki67. Transgenes encoding productively rearranged immunoglobulin heavy light chains complemented deficiency, completely rescuing development. Collectively, these results identify unique contribution from somatic