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Global mapping of c-Myc binding sites and target gene networks in human B cells

Authors
  • Karen I. Zeller
  • XiaoDong Zhao
  • Charlie W. H. Lee
  • Kuo Ping Chiu
  • Fei Yao
  • Jason T. Yustein
  • Hong Sain Ooi
  • Yuriy L. Orlov
  • Atif Shahab
  • How Choong Yong
  • YuTao Fu
  • Zhiping Weng
  • Vladimir A. Kuznetsov
  • Wing-Kin Sung
  • Yijun Ruan
  • Chi V. Dang
  • Chia-Lin Wei
Publisher
National Academy of Sciences
Publication Date
Nov 08, 2006
Source
PMC
Keywords
Disciplines
  • Biology
License
Unknown

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.

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