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

Autori
Sandhu, Kuljeet Singh ; Li, Guoliang ; Poh, Huay Mei ; Quek , Yu Ling Kelly ; Sia , Yee Yen ; Peh, Su Qin ; Mulawadi, Fabianus Hendriyan ; Lim , Joanne ; Šikić, Mile ; Menghi, Francesca ; Thalamuthu, Anbupalam ; Sung , Wing Kin ; Ruan, Xiaoan ; Fullwood, Melissa Jane ; Liu, Edison ; Csermely , Peter ; Ruan, Yijun

Izvornik
Cell Reports (2211-1247) 2 (2012), 5; P1207-1219

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
chromatin ; interactions ; network

Sažetak
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

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Računarstvo

POVEZANOST RADA