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Large-scale functional organization of long-range chromatin interaction networks.

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Sandhu KS,Li G,Poh HM,Quek YL,Sia YY,Peh SQ,Mulawadi FH,Lim J,Sikic M,Menghi F,Thalamuthu A,Sung WK,Ruan X,Fullwood MJ,Liu E,Csermely P,Ruan Y

doi

10.1016/j.celrep.2012.09.022

subject

Has Abstract

pub_date

2012-11-29 00:00:00

pages

1207-19

issue

5

issn

2211-1247

pii

S2211-1247(12)00326-9

journal_volume

2

pub_type

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