Michelotti E F, Sanford S, Levens D
Gene Regulation Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature. 1997 Aug 28;388(6645):895-9. doi: 10.1038/42282.
During development and differentiation, cellular phenotypes are stably propagated through numerous cell divisions. This epigenetic 'cell memory' helps to maintain stable patterns of gene expression. DNA methylation and the propagation of specific chromatin structures may both contribute to cell memory. 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; second, the chromatin state must survive mitosis, when chromatin condenses, transcription is turned off, and almost all double-stranded DNA-binding proteins are displaced. 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.
在发育和分化过程中，细胞表型通过众多细胞分裂得以稳定传播。这种表观遗传的“细胞记忆”有助于维持稳定的基因表达模式。DNA甲基化和特定染色质结构的传播可能都对细胞记忆有贡献。在细胞周期中有两个阻碍因素会妨碍特定染色质构型的遗传：其一，相关结构必须耐受S期DNA复制叉的通过；其二，染色质状态必须在有丝分裂中存活下来，此时染色质凝聚，转录关闭，几乎所有双链DNA结合蛋白都被置换。有丝分裂后，之前表达和沉默基因的模式必须得以恢复。这种恢复可能受质量作用支配，由各个组分的结合亲和力和浓度决定。或者，一部分因子可能仍与有丝分裂染色体结合，提供一个分子书签以指导正确的染色质重新组装。在这里，我们在体内分析有丝分裂期间转录起始位点处的DNA，发现它在计划重新激活的基因中构象扭曲，但在受抑制的基因中未扭曲。这些依赖蛋白质的构象扰动可能通过“标记”基因以便重新表达，从而有助于在有丝分裂后重新建立转录。
