Large-Scale Functional Organization of Long-Range Chromatin Interaction Networks

Sandhu, Kuljeet Singh, Li, Guoliang, Poh, Huay Mei, Quek, Yu Ling Kelly, Sia, Yee Yen, Peh, Su Qin, Mulawadi, Fabianus Hendriyan, Lim, Joanne, Sikic, Mile, Menghi, Francesca, Thalamuthu, Anbupalam, Sung, Wing Kin, Ruan, Xiaoan, Fullwood, Melissa Jane, Liu, Edison, Csermely, Peter and Ruan, Yijun (2012) Large-Scale Functional Organization of Long-Range Chromatin Interaction Networks. Cell Reports, 2 5: 1207-1219. doi:10.1016/j.celrep.2012.09.022

Author Sandhu, Kuljeet Singh
Li, Guoliang
Poh, Huay Mei
Quek, Yu Ling Kelly
Sia, Yee Yen
Peh, Su Qin
Mulawadi, Fabianus Hendriyan
Lim, Joanne
Sikic, Mile
Menghi, Francesca
Thalamuthu, Anbupalam
Sung, Wing Kin
Ruan, Xiaoan
Fullwood, Melissa Jane
Liu, Edison
Csermely, Peter
Ruan, Yijun
Title Large-Scale Functional Organization of Long-Range Chromatin Interaction Networks
Journal name Cell Reports   Check publisher's open access policy
ISSN 2211-1247
Publication date 2012-11-01
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.celrep.2012.09.022
Open Access Status DOI
Volume 2
Issue 5
Start page 1207
End page 1219
Total pages 13
Place of publication Cambridge, MA United States
Publisher Cell Press
Collection year 2013
Language eng
Formatted abstract
Chromatin interactions play important roles in transcription regulation. To better understand the underlying evolutionary and functional constraints of these
interactions, we implemented a systems approach to examine RNA polymerase-II-associated chromatin interactions in human cells. We found that 40% of the total genomic elements involved in chromatin interactions converged to a giant, scale-free-like, hierarchical network organized into chromatin communities.  The communities were enriched in specific functions and were syntenic through evolution.
Disease-associated SNPs from genome-wide association studies were enriched among the nodes with fewer interactions, implying their selection against deleterious interactions by limiting the total number of interactions, a model that we further
reconciled using somatic and germline cancer mutation data. The hubs lacked disease-associated SNPs, constituted a nonrandomly interconnected core of
key cellular functions, and exhibited lethality in mouse mutants, supporting an evolutionary selection that favored the nonrandom spatial clustering of the
least-evolving key genomic domains against random genetic or transcriptional errors in the genome.  Altogether, our analyses reveal a systems-level evolutionary framework that shapes functionally compartmentalized and error-tolerant transcriptional regulation of human genome in three dimensions.
Keyword Cancer Risk Loci
Gene Expression
Biological Networks
Complex Networks
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
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