An oestrogen-receptor-alpha-bound human chromatin interactome.
Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to regulatory DNA elements distant from gene promoters. Although distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Here we describe the development of a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global chromatin interactions, with which we have comprehensively mapped the chromatin interaction network bound by oestrogen receptor alpha (ER-alpha) in the human genome. We found that most high-confidence remote ER-alpha-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-alpha functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.
Fullwood
Melissa J
MJ
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672.
Liu
Mei Hui
MH
Pan
You Fu
YF
Liu
Jun
J
Xu
Han
H
Mohamed
Yusoff Bin
YB
Orlov
Yuriy L
YL
Velkov
Stoyan
S
Ho
Andrea
A
Mei
Poh Huay
PH
Chew
Elaine G Y
EG
Huang
Phillips Yao Hui
PY
Welboren
Willem-Jan
WJ
Han
Yuyuan
Y
Ooi
Hong Sain
HS
Ariyaratne
Pramila N
PN
Vega
Vinsensius B
VB
Luo
Yanquan
Y
Tan
Peck Yean
PY
Choy
Pei Ye
PY
Wansa
K D Senali Abayratna
KD
Zhao
Bing
B
Lim
Kar Sian
KS
Leow
Shi Chi
SC
Yow
Jit Sin
JS
Joseph
Roy
R
Li
Haixia
H
Desai
Kartiki V
KV
Thomsen
Jane S
JS
Lee
Yew Kok
YK
Karuturi
R Krishna Murthy
RK
Herve
Thoreau
T
Bourque
Guillaume
G
Stunnenberg
Hendrik G
HG
Ruan
Xiaoan
X
Cacheux-Rataboul
Valere
V
Sung
Wing-Kin
WK
Liu
Edison T
ET
Wei
Chia-Lin
CL
Cheung
Edwin
E
Ruan
Yijun
Y
D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D003432:Cross-Linking Reagents; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005557:Formaldehyde; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002843:Chromatin; D003432:Cross-Linking Reagents; D047628:Estrogen Receptor alpha; D005557:Formaldehyde