Toward an understanding of the relation between gene regulation and 3D genome organization
- PDF / 1,583,944 Bytes
- 17 Pages / 595.276 x 785.197 pts Page_size
- 57 Downloads / 170 Views
RESEARCH ARTICLE Toward an understanding of the relation between gene regulation and 3D genome organization Hao Tian1, Ying Yang1, Sirui Liu1, Hui Quan1, Yi Qin Gao1,2,3,* 1
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China 2 Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China 3 Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing 100871, China * Correspondence: [email protected] Received April 24, 2020; Revised June 9, 2020; Accepted July 12, 2020 Background: High-order chromatin structure has been shown to play a vital role in gene regulation. Previously we identified two types of sequence domains, CGI (CpG island) forest and CGI prairie, which tend to spatially segregate, but to different extent in different tissues. Here we aim to further quantify the association of domain segregation with gene regulation and therefore differentiation. Methods: By means of the published RNA-seq and Hi-C data, we identified tissue-specific genes and quantitatively investigated how their regulation is relevant to chromatin structure. Besides, two types of gene networks were constructed and the association between gene pair co-regulation and genome organization is discussed. Results: We show that compared to forests, tissue-specific genes tend to be enriched in prairies. Highly specific genes also tend to cluster according to their functions in a relatively small number of prairies. Furthermore, tissue-specific forest-prairie contact formation was associated with the regulation of tissue-specific genes, in particular those in the prairie domains, pointing to the important role of gene positioning, in the linear DNA sequence as well as in 3D chromatin structure, in gene regulatory network formation. Conclusion: We investigated how gene regulation is related to genome organization from the perspective of forestprairie spatial interactions. Since unlike compartments A and B, forest and prairie are identified solely based on sequence properties. Therefore, the simple and uniform framework (forest-prairie domain segregation) provided here can be utilized to further understand the chromatin structure changes as well as the underlying biological significances in different stages, such as tumorgenesis.
Keywords: CGI forest; CGI prairie; domain segregation; chromatin structure; gene regulation Author summary: Growing evidence has revealed the vital role of genome architecture in gene regulation. In this paper, we systematically investigated how genome organization is associated with gene regulation from the perspective of spatial interactions between CGI forest and CGI prairie, two distinct sequence domains. Such structure-function relation appears to be a common phenomenon among all tissues we analyzed, indicating the important roles of forest-prairie domain segregation in gene regulatory network formation and differentiation.
INTRODUCTION Over the last decade, with the development of chro
Data Loading...
