Structural Modeling of Chromatin Integrates Genome Features and Reveals Chromosome Folding Principle

Wen Jun Xie,Xiaoxia Cai,Luming Meng,Sirui Liu,Ling Zhang,Yi Qin Gao

doi:10.1038/s41598-017-02923-6

Wen Jun Xie, Xiaoxia Cai + Show 4 more

Open Access

https://doi.org/10.1038/s41598-017-02923-6

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Abstract

How chromosomes fold into 3D structures and how genome functions are affected or even controlled by their spatial organization remain challenging questions. Hi-C experiment has provided important structural insights for chromosome, and Hi-C data are used here to construct the 3D chromatin structure which are characterized by two spatially segregated chromatin compartments A and B. By mapping a plethora of genome features onto the constructed 3D chromatin model, we show vividly the close connection between genome properties and the spatial organization of chromatin. We are able to dissect the whole chromatin into two types of chromatin domains which have clearly different Hi-C contact patterns as well as different sizes of chromatin loops. The two chromatin types can be respectively regarded as the basic units of chromatin compartments A and B, and also spatially segregate from each other as the two chromatin compartments. Therefore, the chromatin loops segregate in the space according to their sizes, suggesting the excluded volume or entropic effect in chromatin compartmentalization as well as chromosome positioning. Taken together, these results provide clues to the folding principles of chromosomes, their spatial organization, and the resulted clustering of many genome features in the 3D space.

Highlights

Modeling chromatin structure using experimental Hi-C data is indispensable in our understanding of genome properties and is expected to play increasingly important roles[12, 13]
Lamina-associated domain and several histone marks have been mapped onto the modeled chromatin structure in previous studies[19, 20], a more comprehensive analysis of the genome features in the 3D space is in need to understanding the role of 3D chromatin
Chromatin compartmentalization can be viewed as a result of the segregation of chromatin loops or TADs according to their sizes, highlighting the importance of entropy in driving chromatin compartmentalization

Summary

Introduction

Modeling chromatin structure using experimental Hi-C data is indispensable in our understanding of genome properties and is expected to play increasingly important roles[12, 13]. Chromatin compartments have been demonstrated to relate with a variety of genome features, including GC-content, replication timing, DNase I hypersensitivity and histone marks[8, 12, 18]. All these genome features were previously found to colocalize on a linear map, but their spatial distribution is still largely unknown. The modeled 3D chromatin structure presents an integrated view of a large variety of genome features and provides important clues to the chromosome folding principle. We found chromosomes position in the nucleus following this entropy-driven mechanism

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Conclusion