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Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

DNA Shape Patterns and Evolutionary Constraint in Nucleosome Positioning Sequences

The process of wrapping DNA around a nucleosome core particle affects the functions encoded in the underlying sequence. Therefore, it is important to understand the biological signals responsible for nucleosome positioning. Nucleosome positioning is one of the current ‘hot’ issues and the various approaches and hypotheses on what positions nucleosomes are discussed extensively in recent publications, particularly in an issue of this journal devoted exclusively to this sub¬ject (1-12). One of the major factors affecting the nucleosome positioning is DNA sequence. Despite the observation that nucleosome positioning is sequence-directed, the core particle makes no base-specific contacts with DNA. These circumstances suggest that nucleosome positioning may be encoded through DNA structural properties and not necessarily the primary sequence. To study this, we introduce a new algorithm named ORChID2 that uses hydroxyl radical cleavage patterns to predict the single-nucleotide resolution shape of a DNA molecule. Analysis of ORChID2 DNA shape profiles in well-positioned nucleosome sequences reveals a periodic and symmetric pattern. Additionally, there is more information encoded in the DNA shape than the primary sequence. Information content is consistently highest at regions where the minor groove is narrow—suggesting a fundamental property of protein-DNA shape recognition in nucleosome positioning. Finally, we present a new algorithm named Chai2 that measures the single-nucleotide resolution evolutionary conservation of DNA shape. Overlaying Chai2 constraint results on ORChID2 shape profiles in nucleosome positioning sequences reveals interesting evolutionary conservation patterns. We suggest that selective pressure operating on DNA shape can influence nucleosome positioning dynamics, and therefore be a major force in genome evolution.

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Stephen C. J. Parker 1*
Sean M. West2, 3
Eric Bishop4
Remo Rohs5
Barry Honig2
Thomas D. Tullius 4, 6
Elliott H. Margulies 1

1 National Human Genome Research Institute
National Institutes of Health
Bethesda, Maryland, USA
2 Howard Hughes Medical Institute
Center for Computational Biology and Bioinformatics
Department of Biochemistry and Molecular Biophysics
Columbia University
New York, USA
3 Center for Genomics and Systems Biology
Department of Biology
New York Univ.
New York, USA
4 Program in Bioinformatics
Boston University
Boston, MA USA
5 Molecular and Computational Biology Program
Department of Biological Sciences
University of Southern California, Los Angeles, CA, USA
6 Department of Chemistry
Boston University
Boston, MA, USA.

ph: (301) 451-0278
fx: (301) 435-6170
stephen.parker@nih.gov