Ki67 deficiency impedes chromatin accessibility and BCR gene rearrangement

Original paper: rupress.org/je...
Video summary by Zhoujie Ding (Monash University, Australia)
Ding et al. discover a unique requirement for Ki67 in regulating chromatin accessibility in the early stages of lymphocyte development undergoing V(D)J rearrangement, thus ensuring normal immunoglobulin gene recombination, cell maturation and peripheral representation.
Ki67 is a widely used marker for identifying proliferating cells. Here, we discovered that lack of Ki67 did affect normal animal development, however Ki67 deficiency resulted in substantial defects in 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 chromatin accessibility at these checkpoint stages involving a putative enhancer region of the Rag locus. In line with this, mRNA expression of Rag1 was diminished and gene rearrangement was less efficient in the absence of Ki67. When we introduced transgenes encoding productively rearranged immunoglobulin heavy and light chains, this complemented Ki67 deficiency, completely rescuing early B-cell development. Collectively, these results identify a unique contribution from Ki67 to antigen-receptor gene rearrangement during lymphopoiesis.
Keywords: Ki67, gene rearrangement, chromatin accessibility, Rag