Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2
Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2
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DOI：
10.1073/pnas.0611419104
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发表时间：
2007-02-27
影响因子：
11.1
通讯作者：
Stein, Gary S.
中科院分区：
文献类型：
--
作者：
Young, Daniel W.;Hassan, Mohammad Q.;Stein, Gary S.
在细胞分裂期间，转录的停止伴随有丝分裂染色体浓缩。一个基本的生物学问题是如何在有丝分裂过程中保留基因表达模式，以确保后代细胞的表型。我们认为，细胞命运决定转录因子提供了一个表观遗传机制，在细胞分裂过程中的基因表达模式的保留。Runx蛋白是造血、神经、胃肠道和成骨细胞命运所必需的谱系特异性转录因子。在这里，我们表明Runx2蛋白在细胞分裂过程中是稳定的，并在有丝分裂过程中通过序列特异性DNA结合与染色体保持相关。使用siRNA介导的沉默，有丝分裂细胞同步化，和表达谱，我们确定Runx2调节的基因，有丝分裂后调制。新的靶基因参与细胞生长和分化的染色质免疫沉淀验证。重要的是，我们发现在有丝分裂期间，当转录关闭时，Runx2选择性地占据靶基因启动子，Runx2缺陷改变有丝分裂组蛋白修饰。我们得出结论，Runx蛋白在细胞分裂过程中保持表型，以支持后代细胞中基因表达的谱系特异性控制中发挥积极作用。
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 immunoprecipitation. 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.