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dc.titleLarge-Scale Functional Organization of Long-Range Chromatin Interaction Networks
dc.contributor.authorSandhu, K.S.
dc.contributor.authorLi, G.
dc.contributor.authorPoh, H.M.
dc.contributor.authorQuek, Y.L.K.
dc.contributor.authorSia, Y.Y.
dc.contributor.authorPeh, S.Q.
dc.contributor.authorMulawadi, F.H.
dc.contributor.authorLim, J.
dc.contributor.authorSikic, M.
dc.contributor.authorMenghi, F.
dc.contributor.authorThalamuthu, A.
dc.contributor.authorSung, W.K.
dc.contributor.authorRuan, X.
dc.contributor.authorFullwood, M.J.
dc.contributor.authorLiu, E.
dc.contributor.authorCsermely, P.
dc.contributor.authorRuan, Y.
dc.identifier.citationSandhu, K.S., Li, G., Poh, H.M., Quek, Y.L.K., Sia, Y.Y., Peh, S.Q., Mulawadi, F.H., Lim, J., Sikic, M., Menghi, F., Thalamuthu, A., Sung, W.K., Ruan, X., Fullwood, M.J., Liu, E., Csermely, P., Ruan, Y. (2012). Large-Scale Functional Organization of Long-Range Chromatin Interaction Networks. Cell Reports 2 (5) : 1207-1219. ScholarBank@NUS Repository.
dc.description.abstractChromatin 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. It is becoming increasingly clear that genes are not autonomous transcriptional units; instead, they physically interact with one another to coordinate transcriptional regulation. Using a network approach, Ruan and colleagues unravel an evolutionarily constrained systems organization of transcription-associated chromatin in the human genome. Their observations provide a possible chromatin-level explanation for how disease-associated mutations evolve and how key cellular genes escape genetic and transcriptional errors. © 2012 The Authors.
dc.contributor.departmentCOMPUTER SCIENCE
dc.description.sourcetitleCell Reports
Appears in Collections:Staff Publications

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