Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity

被引:36
|
作者
Pancaldi, Vera [1 ]
Carrillo-de-Santa-Pau, Enrique [1 ]
Javierre, Biola Maria [2 ]
Juan, David [1 ]
Fraser, Peter [2 ]
Spivakov, Mikhail [2 ]
Valencia, Alfonso [1 ]
Rico, Daniel [1 ]
机构
[1] Spanish Natl Canc Res Ctr CNIO, Struct Biol & BioComp Programme, Madrid, Spain
[2] Babraham Inst, Nucl Dynam Programme, Cambridge, England
来源
GENOME BIOLOGY | 2016年 / 17卷
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
Assortativity; 3D genome; Chromatin Interaction Network; Embryonic stem cells; Epigenomics; Promoter Capture Hi-C; Enhancers; Polycomb; RNA polymerase; HI-C REVEALS; LONG-RANGE INTERACTIONS; TRANSCRIPTION ELONGATION; PROMOTER INTERACTIONS; ENHANCER; REORGANIZATION; ARCHITECTURE; EXPRESSION; PRINCIPLES; CONTACTS;
D O I
10.1186/s13059-016-1003-3
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Network analysis is a powerful way of modeling chromatin interactions. Assortativity is a network property used in social sciences to identify factors affecting how people establish social ties. We propose a new approach, using chromatin assortativity, to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts. Results: We use high-resolution promoter capture Hi-C and Hi-Cap data as well as ChIA-PET data from mouse embryonic stem cells to investigate promoter-centered chromatin interaction networks and calculate the presence of specific epigenomic features in the chromatin fragments constituting the nodes of the network. We estimate the association of these features with the topology of four chromatin interaction networks and identify features localized in connected areas of the network. Polycomb group proteins and associated histone marks are the features with the highest chromatin assortativity in promoter-centered networks. We then ask which features distinguish contacts amongst promoters from contacts between promoters and other genomic elements. We observe higher chromatin assortativity of the actively elongating form of RNA polymerase 2 (RNAPII) compared with inactive forms only in interactions between promoters and other elements. Conclusions: Contacts among promoters and between promoters and other elements have different characteristic epigenomic features. We identify a possible role for the elongating form of RNAPII in mediating interactions among promoters, enhancers, and transcribed gene bodies. Our approach facilitates the study of multiple genome-wide epigenomic profiles, considering network topology and allowing the comparison of chromatin interaction networks.
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页数:19
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