TBP bookmarks and preserves neural stem cell fate memory by orchestrating local chromatin architecture

Yuying Shen; Kun Liu; Jie Liu; Jingwen Shen; Tongtong Ye; Runxiang Zhao; Rulan Zhang; Yan Song

doi:10.1016/j.molcel.2024.11.019

TBP bookmarks and preserves neural stem cell fate memory by orchestrating local chromatin architecture

Mol Cell. 2024 Dec 5:S1097-2765(24)00944-4. doi: 10.1016/j.molcel.2024.11.019. Online ahead of print.

Authors

Yuying Shen¹, Kun Liu², Jie Liu¹, Jingwen Shen¹, Tongtong Ye¹, Runxiang Zhao¹, Rulan Zhang¹, Yan Song³

Affiliations

¹ Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
² 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.
³ 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. Electronic address: yan.song@pku.edu.cn.

PMID: 39662469
DOI: 10.1016/j.molcel.2024.11.019

Abstract

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.

Keywords: Drosophila melanogaster; EP400; H2A.Z; TBP; cell fate memory; chromatin remodeler; mitotic bookmarking; mitotic retention; neural development; neural stem cell.