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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2
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Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2

机译：细胞命运决定转录因子Runx2的基因表达模式的有丝分裂保留

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摘要

During cell division, cessation of transcription is coupled with mitotic chromosome condensation. A fundamental biological question is how gene expression patterns are retained during mitosis to ensure the phenotype of progeny cells. We suggest that cell fate-determining transcription factors provide an epigenetic mechanism for the retention of gene expression patterns during cell division. Runx proteins are lineage-specific transcription factors that are essential for hematopoietic, neuronal, gastrointestinal, and osteogenic cell fates. Here we show that Runx2 protein is stable during cell division and remains associated with chromosomes during mitosis through sequence-specific DNA binding. Using siRNA-mediated silencing, mitotic cell synchronization, and expression profiling, we identify Runx2-regulated genes that are modulated postmitotically. Novel target genes involved in cell growth and differentiation were validated by chromatin immuno-precipitation. Importantly, we find that during mitosis, when transcription is shut down, Runx2 selectively occupies target gene promoters, and Runx2 deficiency alters mitotic histone modifications. We conclude that Runx proteins have an active role in retaining phenotype during cell division to support lineage-specific control of gene expression in progeny cells.
机译：在细胞分裂过程中，转录的停止与有丝分裂染色体的凝结相结合。一个基本的生物学问题是在有丝分裂过程中如何保留基因表达模式，以确保后代细胞的表型。我们建议确定细胞命运的转录因子提供了一种在细胞分裂过程中保留基因表达模式的表观遗传机制。 Runx蛋白是谱系特异性转录因子，对于造血，神经元，胃肠道和成骨细胞的命运至关重要。在这里，我们显示Runx2蛋白在细胞分裂过程中是稳定的，并且在有丝分裂期间通过序列特异性DNA结合仍与染色体相关。使用siRNA介导的沉默，有丝分裂细胞同步和表达谱，我们确定Runx2调控基因的有丝分裂后被调制。通过染色质免疫沉淀验证了参与细胞生长和分化的新型靶基因。重要的是，我们发现在有丝分裂期间，当转录被关闭时，Runx2选择性地占据了靶基因的启动子，而Runx2缺乏则改变了有丝分裂的组蛋白修饰。我们得出结论，Runx蛋白在细胞分裂过程中具有保持表型的积极作用，以支持后代细胞中基因表达的谱系特异性控制。

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