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Global mapping of c-Myc binding sites and target gene networks in human B cells.by: Karen I. Zeller, XiaoDong Zhao, Charlie W. Lee, Kuo Ping P. Chiu, Fei Yao, Jason T. Yustein, Hong Sain S. Ooi, Yuriy L. Orlov, Atif Shahab, How Choong C. Yong, Yutao Fu, Zhiping Weng, Vladimir A. Kuznetsov, Wing-Kin K. Sung, Yijun Ruan, Chi V. Dang, Chia-Lin L. Wei
Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 47. (21 November 2006), pp. 17834-17839.
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AbstractThe 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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