Integrative analyses shed new light on human ribosomal protein gene regulation.

Xin Li,Xiaoman Li,Haiyan Hu,Yiyu Zheng

doi:10.1038/srep28619

Abstract

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.

Highlights

Ribosomal protein genes (RPGs) are important house-keeping genes that code for the architecture proteins in ribosomes, the machinery responsible for protein synthesis[1]
DNase I hypersensitive sites (DHSs) were used because DHSs indicate open chromatin regions, where regulatory proteins in general bind to regulate their target genes
We assumed that a region was a possible RPG regulatory region, if it was within one megabase neighbourhood of a RPG and overlapped with DHSs across at least a large number of these 349 experiments

Summary

Introduction

Ribosomal protein genes (RPGs) are important house-keeping genes that code for the architecture proteins in ribosomes, the machinery responsible for protein synthesis[1]. To explain the coordinate expression pattern of RPGs, many studies hypothesized and suggested that RPGs in a species may be regulated by the same transcription factors (TFs) and share common motifs in their regulatory regions[13,14,15,16,17]. It is vital to study distal as well as proximal regulatory regions of human RPGs to have a better understanding of their coordinate expression pattern. The high throughput data generated so far provide an unprecedented opportunity to study the transcriptional regulation of human RPGs. The DNase I hypersensitive sites (DHSs) delineate open chromatin regions under an experimental condition, which may indicate the locations of active regulatory regions under this condition[27,28]. Because RPGs are active under every normal condition, the generated DHS, Hi-C, ChIA-PET data, together with other types of data, provide the information of their distal and proximal regulatory regions under various conditions

Methods

Results

Conclusion