Nucleic Acids Research Advance Access originally published online on March 10, 2009
Nucleic Acids Research 2009 37(8):2737-2746; doi:10.1093/nar/gkp124
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Nucleic Acids Research, 2009, Vol. 37, No. 8 2737-2746
© 2009 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 |
Human genomic Z-DNA segments probed by the Z
domain of ADAR1
1Division of Genomics and Genetics, 2Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 and 3Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, PR China
*To whom correspondence should be addressed. Tel: +65 6316 2809; Fax: +65 6791 3856; Email: pdroge{at}ntu.edu.sg
Received October 21, 2008. Revised February 5, 2009. Accepted February 14, 2009.
Double-stranded DNA is a dynamic molecule that adopts different secondary structures. Experimental evidence indicates Z-DNA plays roles in DNA transactions such as transcription, chromatin remodeling and recombination. Furthermore, our computational analysis revealed that sequences with high Z-DNA forming potential at moderate levels of DNA supercoiling are enriched in human promoter regions. However, the actual distribution of Z-DNA segments in genomes of mammalian cells has been elusive due to the unstable nature of Z-DNA and lack of specific probes. Here we present a first human genome map of most stable Z-DNA segments obtained with A549 tumor cells. We used the Z-DNA binding domain, Z
, of the RNA editing enzyme ADAR1 as probe in conjunction with a novel chromatin affinity precipitation strategy. By applying stringent selection criteria, we identified 186 genomic Z-DNA hotspots. Interestingly, 46 hotspots were located in centromeres of 13 human chromosomes. There was a very strong correlation between these hotspots and high densities of single nucleotide polymorphism. Our study indicates that genetic instability and rapid evolution of human centromeres might, at least in part, be driven by Z-DNA segments. Contrary to in silico predictions, however, we found that only two of the 186 hotspots were located in promoter regions.