title: A global map of p53 transcription-factor binding sites in the human genome.
abstract: 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.
authors.affiliation: Genome Institute of Singapore, Singapore 138672.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Wei
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Vinsensius B
authors.initials: VB
authors.lastname: Vega
authors.forename: Kuo Ping
authors.initials: KP
authors.lastname: Chiu
authors.forename: Patrick
authors.initials: P
authors.lastname: Ng
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Atif
authors.initials: A
authors.lastname: Shahab
authors.forename: How Choong
authors.initials: HC
authors.lastname: Yong
authors.forename: YuTao
authors.initials: Y
authors.lastname: Fu
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.forename: JianJun
authors.initials: J
authors.lastname: Liu
authors.forename: Xiao Dong
authors.initials: XD
authors.lastname: Zhao
authors.forename: Joon-Lin
authors.initials: JL
authors.lastname: Chew
authors.forename: Yen Ling
authors.initials: YL
authors.lastname: Lee
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Kuznetsov
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.forename: Bing
authors.initials: B
authors.lastname: Lim
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
authors.forename: Huck-Hui
authors.initials: HH
authors.lastname: Ng
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
mesh_terms: 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
chemical_list: D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA