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Quantitative Biology

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Quant. Biol.    2020, Vol. 8 Issue (4) : 295-311    https://doi.org/10.1007/s40484-020-0221-6
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
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Abstract

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 forest-prairie 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     
Corresponding Author(s): Yi Qin Gao   
Online First Date: 23 November 2020    Issue Date: 24 December 2020
 Cite this article:   
Hao Tian,Ying Yang,Sirui Liu, et al. Toward an understanding of the relation between gene regulation and 3D genome organization[J]. Quant. Biol., 2020, 8(4): 295-311.
 URL:  
https://academic.hep.com.cn/qb/EN/10.1007/s40484-020-0221-6
https://academic.hep.com.cn/qb/EN/Y2020/V8/I4/295
Fig.1  Forest and prairie gene features.
Liver Cortex Hippo Lung LV Spleen Ovary Adrenal Aorta Panc
Ft 217 193 169 67 40 106 43 55 10 128
Fnt 14853 14877 14901 15003 15030 14964 15027 15015 15060 14942
Pt 95 99 77 44 8 58 11 22 4 65
Pnt 3248 3244 3266 3299 3335 3285 3332 3321 3339 3278
p-value 1.1e–7 9.7e–11 6.4e–7 9.5e–8 – 1.3e–7 – 0.025 – 2.4e–7
Tab.1  TSG distribution in forest and prairie domains
Fig.2  The sequence dependence of gene tissue specificity and 3D environment gene located in.
Fig.3  Prairie gene expression regulation and genome organization.
Fig.4  The interplay between gene pair expression coordination and chromatin structure.
HKG housekeeping gene
TSG tissue-specific gene
TF transcription factor
CGI CpG island
F CGI forest
P CGI prairie
TAD topologically associated domain
Hi-C high throughput chromosome conformation capture
ChIA-PET chromatin interaction analysis by paired-end tag sequencing
H3K9me3 histone H3 lysine 9 trimethylation
PCC Pearson correlation coefficient
  
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