School of Data and Computer Science, Sun Yat-Sen University, Guangzhou 510006, China.
Guangdong Province Key Laboratory of Big Data Analysis and Processing, Sun Yat-Sen University, Guangzhou 510006, China.
Cells. 2019 Jul 20;8(7):754. doi: 10.3390/cells8070754.
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.
已经使用了各种类型的数据，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，来破译 TF 调控机制。然而，大多数受特定 TF 敲除影响的基因不受该因子的结合。在这里，我表明通过考虑 TF 敲除影响的基因和 TF 结合的基因的核定位，可以部分解释这个有趣的结果。我发现，具有统计学意义的数量的 TF 敲除影响的基因与相应 TF 结合的基因表现出核共定位。尽管这些 TF 敲除影响的基因不直接被相应的 TF 结合；但 TF 往往与直接结合这些基因的 TF 处于相同的细胞成分中。TF 敲除影响的基因表现出共表达，并与相应 TF 结合的空间相邻基因参与相同的生物过程。这些结果表明，TF 可以通过核共定位而无需直接 DNA 结合来调节基因，补充了 TF 通过直接结合 DNA 来调节基因的传统观点。我的发现将对理解 TF 调控机制产生影响。
