Global mapping of c-Myc binding sites and target gene networks in human B cells.
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.
Zeller
Karen I
KI
Department of Medicine and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Zhao
XiaoDong
X
Lee
Charlie W H
CW
Chiu
Kuo Ping
KP
Yao
Fei
F
Yustein
Jason T
JT
Ooi
Hong Sain
HS
Orlov
Yuriy L
YL
Shahab
Atif
A
Yong
How Choong
HC
Fu
Yutao
Y
Weng
Zhiping
Z
Kuznetsov
Vladimir A
VA
Sung
Wing-Kin
WK
Ruan
Yijun
Y
Dang
Chi V
CV
Wei
Chia-Lin
CL
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
D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors