Shen Yuying, Liu Kun, Liu Jie, Shen Jingwen, Ye Tongtong, Zhao Runxiang, Zhang Rulan, Song Yan
Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
Mol Cell. 2025 Jan 16;85(2):413-429.e10. doi: 10.1016/j.molcel.2024.11.019. Epub 2024 Dec 10.
Mitotic bookmarking has been posited as an important strategy for cells to faithfully propagate their fate memory through cell generations. However, the physiological significance and regulatory mechanisms of mitotic bookmarking in neural development remain unexplored. Here, we identified TATA-binding protein (TBP) as a crucial mitotic bookmarker for preserving the fate memory of Drosophila neural stem cells (NSCs). Phosphorylation by the super elongation complex (SEC) is important for TBP to retain as discrete foci at mitotic chromosomes of NSCs to effectively transmit their fate memory. TBP depletion leads to drastic NSC loss, whereas TBP overexpression enhances the ability of SEC to induce neural progenitor dedifferentiation and tumorigenesis. Importantly, TBP achieves its mitotic retention through recruiting the chromatin remodeler EP400, which in turn increases local chromatin accessibility via depositing H2A.Z. Thus, local chromatin remodeling ensures mitotic bookmarking, which may represent a general principle underlying the preservation of cell fate memory.
有丝分裂标记被认为是细胞通过细胞世代忠实地传递其命运记忆的重要策略。然而，有丝分裂标记在神经发育中的生理意义和调控机制仍未得到探索。在这里，我们确定了TATA结合蛋白（TBP）是果蝇神经干细胞（NSC）命运记忆保留的关键有丝分裂标记。超延伸复合物（SEC）的磷酸化对于TBP在NSC有丝分裂染色体上保留为离散焦点以有效传递其命运记忆很重要。TBP缺失导致NSC大量损失，而TBP过表达增强了SEC诱导神经祖细胞去分化和肿瘤发生的能力。重要的是，TBP通过招募染色质重塑因子EP400实现其有丝分裂保留，EP400进而通过沉积H2A.Z增加局部染色质可及性。因此，局部染色质重塑确保了有丝分裂标记，这可能代表了细胞命运记忆保留的一个普遍原则。
