首页> 外文期刊>Gene expression >Transcriptional profiling of the cell cycle checkpoint gene kruppel-like factor 4 reveals a global inhibitory function in macromolecular biosynthesis.
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Transcriptional profiling of the cell cycle checkpoint gene kruppel-like factor 4 reveals a global inhibitory function in macromolecular biosynthesis.

机译:细胞周期检查点基因kruppel样因子4的转录分析揭示了大分子生物合成中的全局抑制功能。

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Kruppel-like factor 4 (KLF4; also known as gut-enriched Kruppel-like factor or GKLF) is known to exhibit checkpoint function during the G1/S and G2/M transitions of the cell cycle. The mechanism by which KLF4 exerts these effects is not fully established. Here we investigated the expression profile of KLF4 in an inducible system over a time course of 24 h. Using oligonucleotide microarrays, we determined that the fold changes relative to control in expression levels of KLF4 exhibited a time-dependent increase from 3- to 20-fold between 4 and 24 h following KLF4 induction. During this period and among a group of 473 cell cycle regulatory genes examined, 96 were positively correlated and 86 were negatively correlated to KLF4's expression profile. Examples of upregulated cell cycle genes include those encoding tumor suppressors such as MCC and FHIT, and cell cycle inhibitors such as CHES1 and CHEK1. Examples of downregulated genes include those that promote the cell cycle including several cyclins and those required for DNA replication. Unexpectedly, several groups of genes involved in macromolecular synthesis, including protein biosynthesis, transcription, and cholesterol biosynthesis, were also significantly inhibited by KLF4. Thus, KLF4 exerts a global inhibitory effect on macromolecular biosynthesis that is beyond its established role as a cell cycle inhibitor.
机译:已知Kruppel样因子4(KLF4;也称为富含肠道的Kruppel样因子或GKLF)在细胞周期的G1 / S和G2 / M转换过程中表现出检查点功能。 KLF4发挥这些作用的机制尚未完全确定。在这里,我们研究了在24小时内可诱导系统中KLF4的表达谱。使用寡核苷酸微阵列,我们确定相对于对照的KLF4表达水平的倍数变化在KLF4诱导后4至24小时之间表现出3至20倍的时间依赖性增加。在此期间,在检查的473个细胞周期调节基因中,有96个与KLF4的表达谱呈正相关,有86个与KLF4的表达谱呈负相关。上调的细胞周期基因的例子包括编码诸如MCC和FHIT之类的肿瘤抑制因子,以及诸如CHES1和CHEK1之类的细胞周期抑制剂的基因。下调的基因的例子包括促进细胞周期的基因,包括几种细胞周期蛋白,以及那些DNA复制所需的基因。出乎意料的是,参与大分子合成的几组基因,包括蛋白质生物合成,转录和胆固醇生物合成,也被KLF4显着抑制。因此,KLF4对大分子生物合成具有全局抑制作用,这已超出其作为细胞周期抑制剂的既定作用。

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