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Nucleic Acids Research Advance Access originally published online on May 21, 2008
Nucleic Acids Research 2008 36(11):3828-3833; doi:10.1093/nar/gkn189
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Nucleic Acids Research, 2008, Vol. 36, No. 11 3828-3833
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Discovery of novel tumor suppressor p53 response elements using information theory

Ilya G. Lyakhov1, Annangarachari Krishnamachari2 and Thomas D. Schneider3,*

1Basic Research Program, SAIC-Frederick, Inc., NCI at Frederick, Frederick, MD, USA, 2Bioinformatics Centre, Jawaharlal Nehru University, New Delhi -110067, India and 3Center for Cancer Research Nanobiology Program, NCI at Frederick, Frederick, MD, USA

*To whom correspondence should be addressed. Tel: +1 301 846 5581;Fax: +1 301 846 5598; Email: toms{at}ncifcrf.gov

Received January 7, 2008. Revised March 31, 2008. Accepted April 1, 2008.

An accurate method for locating genes under tumor suppressor p53 control that is based on a well-established mathematical theory and built using naturally occurring, experimentally proven p53 sites is essential in understanding the complete p53 network. We used a molecular information theory approach to create a flexible model for p53 binding. By searching around transcription start sites in human chromosomes 1 and 2, we predicted 16 novel p53 binding sites and experimentally demonstrated that 15 of the 16 (94%) sites were bound by p53. Some were also bound by the related proteins p63 and p73. Thirteen of the adjacent genes were controlled by at least one of the proteins. Eleven of the 16 sites (69%) had not been identified previously. This molecular information theory approach can be extended to any genetic system to predict new sites for DNA-binding proteins.


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