Espinal-Enríquez Jesús, González-Terán Daniel, Hernández-Lemus Enrique
Computational Genomics Division, National Institute of Genomic Medicine, 14610 México City, Mexico.
Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, 04510 México City, Mexico.
Int J Genomics. 2017;2017:4858173. doi: 10.1155/2017/4858173. Epub 2017 Sep 30.
Understanding the general principles underlying genetic regulation in eukaryotes is an incomplete and challenging endeavor. The lack of experimental information regarding the regulation of the whole set of transcription factors and their targets in different cell types is one of the main reasons to this incompleteness. So far, there is a small set of curated known interactions between transcription factors and their downstream genes. Here, we built a transcription factor network for human monocytic THP-1 myeloid cells based on the experimentally curated database where nodes are genes and the experimental interactions correspond to links. We present the topological parameters which define the network as well as some global structural features and introduce a relative inuence parameter to quantify the relevance of a transcription factor in the context of induction of a phenotype. Genes like ZHX2, ADNP, or SMAD6 seem to be highly regulated to avoid an avalanche transcription event. We compare these results with those of , a highly curated transcriptional network for the prokaryotic organism , finding similarities between general hallmarks on both transcriptional programs. We believe that an approach, such as the one shown here, could help to understand the one regulation of transcription in eukaryotic cells.
了解真核生物基因调控的一般原则是一项不完整且具有挑战性的工作。缺乏关于不同细胞类型中整套转录因子及其靶标的调控的实验信息是造成这种不完整性的主要原因之一。到目前为止,转录因子与其下游基因之间只有一小部分经过精心整理的已知相互作用。在此,我们基于经过实验整理的数据库构建了人类单核细胞THP-1髓样细胞的转录因子网络,其中节点是基因,实验相互作用对应于链接。我们展示了定义该网络的拓扑参数以及一些全局结构特征,并引入了一个相对影响参数来量化转录因子在表型诱导背景下的相关性。像ZHX2、ADNP或SMAD6这样的基因似乎受到高度调控以避免雪崩式转录事件。我们将这些结果与针对原核生物精心整理的转录网络的结果进行比较,发现这两个转录程序的一般特征之间存在相似性。我们相信,如此处所示的方法有助于理解真核细胞中转录的调控。