A global map of p53 transcription-factor binding sites in the human genome.
The ability to derive a whole-genome map of transcription-factor binding sites (TFBS) is crucial for elucidating gene regulatory networks. Herein, we describe a robust approach that couples chromatin immunoprecipitation (ChIP) with the paired-end ditag (PET) sequencing strategy for unbiased and precise global localization of TFBS. We have applied this strategy to map p53 targets in the human genome. From a saturated sampling of over half a million PET sequences, we characterized 65,572 unique p53 ChIP DNA fragments and established overlapping PET clusters as a readout to define p53 binding loci with remarkable specificity. Based on this information, we refined the consensus p53 binding motif, identified at least 542 binding loci with high confidence, discovered 98 previously unidentified p53 target genes that were implicated in novel aspects of p53 functions, and showed their clinical relevance to p53-dependent tumorigenesis in primary cancer samples.
Wei
Chia-Lin
CL
Genome Institute of Singapore, Singapore 138672.
Wu
Qiang
Q
Vega
Vinsensius B
VB
Chiu
Kuo Ping
KP
Ng
Patrick
P
Zhang
Tao
T
Shahab
Atif
A
Yong
How Choong
HC
Fu
YuTao
Y
Weng
Zhiping
Z
Liu
JianJun
J
Zhao
Xiao Dong
XD
Chew
Joon-Lin
JL
Lee
Yen Ling
YL
Kuznetsov
Vladimir A
VA
Sung
Wing-Kin
WK
Miller
Lance D
LD
Lim
Bing
B
Liu
Edison T
ET
Yu
Qiang
Q
Ng
Huck-Hui
HH
Ruan
Yijun
Y
D001665:Binding Sites / Q000235:genetics; D047369:Chromatin Immunoprecipitation / Q000379:methods; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D015894:Genome, Human; D045325:HCT116 Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA