Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.M109.014563
Title: Deregulated direct targets of the hepatitis B virus (HBV) protein, HBx, identified through chromatin immunoprecipitation and expression microarray profiling
Authors: Sung, W.-K. 
Lu, Y.
Lee, C.W.H.
Zhang, D.
Ronaghi, M.
Lee, C.G.L.
Issue Date: 2009
Citation: Sung, W.-K., Lu, Y., Lee, C.W.H., Zhang, D., Ronaghi, M., Lee, C.G.L. (2009). Deregulated direct targets of the hepatitis B virus (HBV) protein, HBx, identified through chromatin immunoprecipitation and expression microarray profiling. Journal of Biological Chemistry 284 (33) : 21941-21954. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M109.014563
Abstract: The hepatitis B-X (HBx) protein is strongly associated with hepatocellular carcinoma. It is implicated not to directly cause cancer but to play a role in hepatocellular carcinoma as a co-factor. The oncogenic potential of HBx primarily lies in its interaction with transcriptional regulators resulting in aberrant gene expression and deregulated cellular pathways. Utilizing ultraviolet irradiation to simulate a tumor-initiating event, we integrated chip-based chromatin immunoprecipitation (ChIP-chip) with expression microarray profiling and identified 184 gene targets directly deregulated by HBx. One-hundred forty-four transcription factors interacting with HBx were computationally inferred. We experimentally validated that HBx interacts with some of the predicted transcription factors (pTF) as well as the promoters of the deregulated target genes of these pTFs. Significantly, we demonstrated that the pTF interacts with the promoters of the deregulated HBx target genes and that deregulation by HBx of these HBx target genes carrying the pTF consensus sequences can be reversed using pTF small interfering RNAs. The roles of these deregulated direct HBx target genes and their relevance in cancer was inferred via querying against biogroup/cancer-related microarray databases using web-based NextBio™ software. Six pathways, including the Jak-STAT pathway, were predicted to be significantly deregulated when HBx binds indirectly to direct target gene promoters. In conclusion, this study represents the first ever demonstration of the utilization of ChIP-chip to identify deregulated direct gene targets from indirect protein-DNA binding as well as transcriptional factors directly interacting with HBx. Increased knowledge of the gene/transcriptional factor targets of HBx will enhance our understanding of the role of HBx in hepatocellular carcinogenesis and facilitate the design of better strategies in combating hepatitis B virus-associated hepatocellular carcinoma. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/38989
ISSN: 00219258
DOI: 10.1074/jbc.M109.014563
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

32
checked on Jul 11, 2018

WEB OF SCIENCETM
Citations

30
checked on Jul 3, 2018

Page view(s)

52
checked on May 19, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.