Nucleic Acids Research Advance Access originally published online on April 16, 2007
Nucleic Acids Research 2007 35(9):2986-3001; doi:10.1093/nar/gkm192
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2007, Vol. 35, No. 9 2986-3001
© 2007 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.
Genomics |
Sequence analysis of p53 response-elements suggests multiple binding modes of the p53 tetramer to DNA targets
1Basic Research Program, SAIC-Frederick Inc., Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA, 2Institute for Advanced Study, Einstein Drive, Princeton, NJ 08540, USA and 3Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
*To whom correspondence should be addressed. Tel: +1-301-846-6540; Fax: +1-301-846-5598; Email: mab{at}ncifcrf.gov
Received November 19, 2006. Revised March 11, 2007. Accepted March 17, 2007.
The p53 tetramer recognizes specifically a 20-bp DNA element. Here, we examined symmetries encoded in p53 response elements (p53REs). We analyzed base inversion correlations within the half-site, as well as in the full-site palindrome. We found that p53REs are not only direct repeats of half-sites; rather, two p53 half-sites couple to form a higher order 20 bp palindrome. The palindrome couplings between the half-sites are stronger for the human than for the mouse genome. The full-site palindrome and half-site palindrome are controlled by insertions between the two half-sites. The most notable feature is that the full-site palindrome with coupling between quarter-sites one and four (H14 coupling) dominates the p53REs without insertions. The most frequently observed insertion in human p53REs of 3 bp enhances the half-site palindrome. The statistical frequencies of the coupling between the half-sites in the human genome correlate with grouped experimental p53 affinities with p53REs. Examination of known p53REs indicates the H14 couplings are stronger for positive regulation than for negatively regulated p53REs, with repressors having the lowest H14 couplings. We propose that the palindromic sequence couplings may encode such potential preferred multiple binding modes of the p53 tetramer to DNA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. B. Veprintsev and A. R. Fersht Algorithm for prediction of tumour suppressor p53 affinity for binding sites in DNA Nucleic Acids Res., March 1, 2008; 36(5): 1589 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ma and A. J. Levine Probing potential binding modes of the p53 tetramer to DNA based on the symmetries encoded in p53 response elements Nucleic Acids Res., December 3, 2007; 35(22): 7733 - 7747. [Abstract] [Full Text] [PDF]
|
|