Differential effect of H1 variant overexpression on cell cycle progression and gene expression
Differential effect of H1 variant overexpression on cell cycle progression and gene expression
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DOI：
10.1093/nar/24.3.486
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发表时间：
1996-02-01
影响因子：
14.9
通讯作者：
Sittman, DB
中科院分区：
文献类型：
--
作者：
Brown, DT;Alexander, BT;Sittman, DB
为了鉴定哺乳动物 H1 接头组蛋白的非等位基因变体之间的功能差异，开发了一种在体内过表达单个 H1 变体的系统，用包含 H1c 或 H1(0) 变体编码区的表达载体转化小鼠 3T3 细胞，该表达载体在诱导型启动子的控制下，形成稳定的单菌落转化体，其中 H1 变体的正常化学计量为 受到干扰，表现出正常的活力，形态未改变，没有长期生长停滞，然而，在细胞周期转化体的不同点从同步释放后，显着过量生产 H1(0)，表现出对 G(1) 和 S 期进展的短暂抑制，H1c 的过度表达至可比水平对细胞周期进展没有影响，对几个细胞周期调节和管家基因的转录水平的分析表明 H1(0) 的过度表达导致所有测试基因的表达显着降低。令人惊讶的是，H1c 的过度表达达到可比水平导致转录水平的影响可以忽略不计，或者在某些情况下导致转录水平显着增加。这些结果支持 H1 变体之间存在功能差异的建议。
To identify functional differences among non-allelic variants of the mammalian H1 linker histones a system for the overexpression of individual H1 variants in vivo was developed, Mouse 3T3 cells were transformed with an expression vector containing the coding regions for the H1c or H1(0) variant under the control of an inducible promoter, Stable, single colony transformants, in which the normal stoichiometry of H1 variants was perturbed, displayed normal viability, unaltered morphology and no long-term growth arrest, However, upon release from synchronization at different points in the cell cycle transformants significantly overproducing H1(0) exhibited transient inhibition of both G(1) and S phase progression, Overexpression of H1c to comparable levels had no effect on cell cycle progression, Analysis of transcript levels for several cell cycle-regulated and housekeeping genes indicated that overexpression of H1(0) resulted in significantly reduced expression of all genes tested, Surprisingly, overexpression of H1c to comparable levels resulted in either a negligible effect or, in some cases, a dramatic increase in transcript levels, These results support the suggestion that functional differences exist among H1 variants.