Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in Pluripotent Stem Cells.
Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in Pluripotent Stem Cells.
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DOI：
10.1016/j.celrep.2017.04.067
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发表时间：
2017-05-16
期刊：
影响因子：
8.8
通讯作者：
Apostolou E
中科院分区：
文献类型：
--
作者：
Liu Y;Pelham-Webb B;Di Giammartino DC;Li J;Kim D;Kita K;Saiz N;Garg V;Doane A;Giannakakou P;Hadjantonakis AK;Elemento O;Apostolou E
在有丝分裂过程中，转录停止，许多染色质特征丢失，对细胞身份的连续性提出了挑战，特别是在快速循环的干细胞中，它们不断平衡自我更新和分化。本研究表明，在多能干细胞中，某些组蛋白标记和干细胞调节因子仍然与有丝分裂染色质的特定基因组区域相关，这种现象被称为有丝分裂书签。干细胞相关基因的增强子被H3K27ac和主调控子OCT4、SOX2和KLF4标记，而管家基因的启动子以细胞类型不变的方式保持高水平的有丝分裂H3K27ac。在有丝分裂结束时，OCT4的时间降解损害了其维持和诱导多能性的能力，这表明其调节功能部分取决于其书签活性。总之，我们的数据记录了组蛋白修饰和转录因子在细胞分裂后促进忠实和有效的干细胞增殖的广泛而特异性的书签。
During mitosis, transcription is halted and many chromatin features are lost, posing a challenge for the continuity of cell identity, particularly in fast cycling stem cells, which constantly balance self-renewal with differentiation. Here we show that, in pluripotent stem cells, certain histone marks and stem cell regulators remain associated with specific genomic regions of mitotic chromatin, a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes are bookmarked by both H3K27ac and the master regulators OCT4, SOX2 and KLF4, while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a cell-type invariant manner. Temporal degradation of OCT4 during mitotic exit compromises its ability both to maintain and induce pluripotency, suggesting that its regulatory function partly depends on its bookmarking activity. Together, our data document a widespread yet specific bookmarking by histone modifications and transcription factors promoting faithful and efficient propagation of stemness after cell division.