Department of Electrical Engineering &Computer Science, University of Central Florida, Orlando, FL, 32816, USA.
Burnett School of Biomedical Science, University of Central Florida, Orlando, FL, 32816, USA.
Sci Rep. 2016 Jun 27;6:28619. doi: 10.1038/srep28619.
Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals.
核糖体蛋白基因(RPGs)是重要的管家基因,其协调表达是众所周知的。先前关于 RPGs 的研究主要局限于它们的启动子区域。最近的高通量研究提供了一个前所未有的机会来研究人类 RPGs 是如何被转录调节的,以及这种转录调节如何有助于各种组织和细胞类型中基因的协调表达。通过分析在 349 种实验条件下的 DNA 酶 I 超敏位点,我们预测了人类基因组中的 217 个 RPG 调控区。这些计算预测的调控区中,超过 86.6%的部分得到了独立实验测量的部分证实。对这些预测的调控区的基序分析确定了 31 个 DNA 基序,其中包括文献中 57.1%经实验验证的调节 RPGs 的基序。有趣的是,我们观察到大多数预测的基序都被同一 RPG 的预测远端和近端调控区共享,这可能是增强子-启动子相互作用的一般机制。我们还发现,RPGs 在不同的细胞中可能受到不同的调节,这表明需要发现和研究特定条件下的 RPG 调控区。我们的研究推进了对 RPGs 如何协调调节的理解,这为哺乳动物基因转录调节的一般原则提供了启示。