title: Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation.
abstract: Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells.
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Republic of Singapore.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Ruan
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Auerbach
authors.forename: Kuljeet Singh
authors.initials: KS
authors.lastname: Sandhu
authors.forename: Meizhen
authors.initials: M
authors.lastname: Zheng
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Huay Mei
authors.initials: HM
authors.lastname: Poh
authors.forename: Yufen
authors.initials: Y
authors.lastname: Goh
authors.forename: Joanne
authors.initials: J
authors.lastname: Lim
authors.forename: Jingyao
authors.initials: J
authors.lastname: Zhang
authors.forename: Hui Shan
authors.initials: HS
authors.lastname: Sim
authors.forename: Su Qin
authors.initials: SQ
authors.lastname: Peh
authors.forename: Fabianus Hendriyan
authors.initials: FH
authors.lastname: Mulawadi
authors.forename: Chin Thing
authors.initials: CT
authors.lastname: Ong
authors.forename: Yuriy L
authors.initials: YL
authors.lastname: Orlov
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Hong
authors.forename: Zhizhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Steve
authors.initials: S
authors.lastname: Landt
authors.forename: Debasish
authors.initials: D
authors.lastname: Raha
authors.forename: Ghia
authors.initials: G
authors.lastname: Euskirchen
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Wei
authors.forename: Weihong
authors.initials: W
authors.lastname: Ge
authors.forename: Huaien
authors.initials: H
authors.lastname: Wang
authors.forename: Carrie
authors.initials: C
authors.lastname: Davis
authors.forename: Katherine I
authors.initials: KI
authors.lastname: Fisher-Aylor
authors.forename: Ali
authors.initials: A
authors.lastname: Mortazavi
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.forename: Thomas
authors.initials: T
authors.lastname: Gingeras
authors.forename: Barbara
authors.initials: B
authors.lastname: Wold
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Fullwood
authors.forename: Edwin
authors.initials: E
authors.lastname: Cheung
authors.forename: Edison
authors.initials: E
authors.lastname: Liu
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
mesh_terms: D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D012319:RNA Polymerase II