Marking of active genes on mitotic chromosomes
Marking of active genes on mitotic chromosomes
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DOI：
10.1038/42282
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发表时间：
1997-08-28
期刊：
影响因子：
64.8
通讯作者：
Levens, D
中科院分区：
文献类型：
--
作者：
Michelotti, EF;Sanford, S;Levens, D
在发育和分化过程中，细胞表型通过多次细胞分裂稳定繁殖（1）。这种表观遗传的“细胞记忆”有助于维持基因表达的稳定模式（2）。DNA甲基化（3）和特定染色质结构的繁殖都可能有助于细胞记忆（4）。在细胞周期中，有两个障碍可以阻碍特定染色质构型的遗传：首先，相关结构必须承受S期DNA复制叉的通过（5）;其次，染色质状态必须在有丝分裂中存活，当染色质浓缩时，转录被关闭，几乎所有双链DNA结合蛋白被置换（6，7）。有丝分裂后，必须恢复先前表达和沉默基因的模式。这种恢复可能受质量作用控制，由单个组分的结合亲和力和浓度决定。或者，因子的子集可能保持与有丝分裂染色体结合，提供分子书签来指导正确的染色质重组，在这里，我们分析了体内有丝分裂过程中转录起始位点的DNA，发现它在预定重新激活的基因中是构象扭曲的，但在抑制的基因中是不扭曲的。基因.这些蛋白质依赖的构象扰动可以帮助重新建立有丝分裂后的转录“标记”基因的重新表达。
During development and differentiation, cellular phenotypes are stably propagated through numerous cell divisions(1). This epigenetic 'cell memory' helps to maintain stable patterns of gene expression(2). DNA methylation(3) and the propagation of specific chromatin structures may both contribute to cell memory(4). There are two impediments during the cell cycle that can hinder the inheritance of specific chromatin configurations: first, the pertinent structures must endure the passage of DNA-replication forks in S phase(5); second, the chromatin state must survive mitosis, when chromatin condenses, transcription is turned off, and almost all double-stranded DNA-binding proteins are displaced(6,7). After mitosis, the previous pattern of expressed and silent genes must be restored. This restoration might be governed by mass action, determined by the binding affinities and concentrations of individual components, Alternatively, a subset of factors might remain bound to mitotic chromosomes, providing a molecular bookmark to direct proper chromatin reassembly, Here we analyse DNA at transcription start sites during mitosis in vivo and find that it is conformationally distorted in genes scheduled for reactivation but is undistorted in repressed genes. These protein-dependent conformational perturbations could help to re-establish transcription after mitosis by 'marking' genes for re-expression.