title: Global mapping of c-Myc binding sites and target gene networks in human B cells.
abstract: The protooncogene MYC encodes the c-Myc transcription factor that regulates cell growth, cell proliferation, cell cycle, and apoptosis. Although deregulation of MYC contributes to tumorigenesis, it is still unclear what direct Myc-induced transcriptomes promote cell transformation. Here we provide a snapshot of genome-wide, unbiased characterization of direct Myc binding targets in a model of human B lymphoid tumor using ChIP coupled with pair-end ditag sequencing analysis (ChIP-PET). Myc potentially occupies > 4,000 genomic loci with the majority near proximal promoter regions associated frequently with CpG islands. Using gene expression profiles with ChIP-PET, we identified 668 direct Myc-regulated gene targets, including 48 transcription factors, indicating that Myc is a central transcriptional hub in growth and proliferation control. This first global genomic view of Myc binding sites yields insights of transcriptional circuitries and cis regulatory modules involving Myc and provides a substantial framework for our understanding of mechanisms of Myc-induced tumorigenesis.
authors.affiliation: Department of Medicine and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Karen I
authors.initials: KI
authors.lastname: Zeller
authors.forename: XiaoDong
authors.initials: X
authors.lastname: Zhao
authors.forename: Charlie W H
authors.initials: CW
authors.lastname: Lee
authors.forename: Kuo Ping
authors.initials: KP
authors.lastname: Chiu
authors.forename: Fei
authors.initials: F
authors.lastname: Yao
authors.forename: Jason T
authors.initials: JT
authors.lastname: Yustein
authors.forename: Hong Sain
authors.initials: HS
authors.lastname: Ooi
authors.forename: Yuriy L
authors.initials: YL
authors.lastname: Orlov
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: Vladimir A
authors.initials: VA
authors.lastname: Kuznetsov
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Chi V
authors.initials: CV
authors.lastname: Dang
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Wei
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation / Q000379:methods; D002874:Chromosome Mapping; D018899:CpG Islands; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D017422:Sequence Analysis, DNA / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors