Transcription Factors Indirectly Regulate Genes through Nuclear Colocalization
Transcription Factors Indirectly Regulate Genes through Nuclear Colocalization
复制标题
转录因子通过核共定位间接调节基因
DOI：
10.3390/cells8070754
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发表时间：
2019-07-01
期刊：
影响因子：
6
通讯作者：
Dai, Zhiming
中科院分区：
文献类型：
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作者：
Dai, Zhiming
各种类型的数据，包括基因组序列、转录因子(TF)敲除数据、TF-DNA相互作用和表达谱，已被用于破译TF的调节机制。然而，大多数受特定转铁蛋白基因敲除影响的基因并不受该因子的限制。在这里，我证明了这个有趣的结果可以通过考虑受Tf基因敲除影响的基因和Tf结合基因的核定位来部分解释。我发现有大量受Tf基因敲除影响的基因在统计学上表现出与相应Tf结合的基因的核共定位。尽管这些受Tf基因敲除影响的基因并不直接与相应的Tf结合，但Tf往往与直接结合这些基因的Tf在同一细胞成分中。受Tf基因敲除影响的基因表现为共表达，并倾向于与空间上相邻的受相应Tf结合的基因参与相同的生物学过程。这些结果表明，转录因子可以通过核共定位来调控基因，而不是直接与DNA结合，补充了传统的转录因子直接结合DNA来调控基因的观点。我的发现将对理解转铁蛋白的调节机制有一定的意义。
Various types of data, including genomic sequences, transcription factor (TF) knockout data, TF-DNA interaction and expression profiles, have been used to decipher TF regulatory mechanisms. However, most of the genes affected by knockout of a particular TF are not bound by that factor. Here, I showed that this interesting result can be partially explained by considering the nuclear positioning of TF knockout affected genes and TF bound genes. I found that a statistically significant number of TF knockout affected genes show nuclear colocalization with genes bound by the corresponding TF. Although these TF knockout affected genes are not directly bound by the corresponding TF; the TF tend to be in the same cellular component with the TFs that directly bind these genes. TF knockout affected genes show co-expression and tend to be involved in the same biological process with the spatially adjacent genes that are bound by the corresponding TF. These results demonstrate that TFs can regulate genes through nuclear colocalization without direct DNA binding, complementing the conventional view that TFs directly bind DNA to regulate genes. My findings will have implications in understanding TF regulatory mechanisms.