Local DNA topography correlates with functional noncoding regions of the human genome. Export

@article{citeulike:4170553, abstract = {The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species, using hydroxyl radical cleavage patterns to interrogate the solvent-accessible surface area of DNA. This algorithm found that 12\% of bases in the human genome are evolutionarily constrained-double the number detected by nucleotide sequence-based algorithms. Topography-informed constrained regions correlated with functional noncoding elements, including enhancers, better than did regions identified solely on the basis of nucleotide sequence. These results support the idea that the molecular shape of DNA is under selection and can identify evolutionary history.}, author = {Parker, Stephen C. and Hansen, Loren and Abaan, Hatice Ozel O. and Tullius, Thomas D. and Margulies, Elliott H.}, citeulike-article-id = {4170553}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1169050}, citeulike-linkout-1 = {http://www.sciencemag.org/content/1169050/.abstract}, citeulike-linkout-2 = {http://www.sciencemag.org/content/1169050/.full.pdf}, citeulike-linkout-3 = {http://www.sciencemag.org/cgi/content/abstract/1169050//}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/19286520}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=19286520}, day = {17}, doi = {10.1126/science.1169050}, issn = {1095-9203}, journal = {Science (New York, N.Y.)}, keywords = {annotation, chromosome, conservation, dna, evolution, structure}, month = {April}, number = {5925}, pages = {389--392}, posted-at = {2009-04-17 16:18:24}, priority = {3}, title = {Local DNA topography correlates with functional noncoding regions of the human genome.}, url = {http://dx.doi.org/10.1126/science.1169050}, volume = {324}, year = {2009} }

TY - JOUR ID - citeulike:4170553 L3 - citeulike-article-id:4170553 N2 - The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species, using hydroxyl radical cleavage patterns to interrogate the solvent-accessible surface area of DNA. This algorithm found that 12% of bases in the human genome are evolutionarily constrained-double the number detected by nucleotide sequence-based algorithms. Topography-informed constrained regions correlated with functional noncoding elements, including enhancers, better than did regions identified solely on the basis of nucleotide sequence. These results support the idea that the molecular shape of DNA is under selection and can identify evolutionary history. IS - 5925 JF - Science (New York, N.Y.) SN - 1095-9203 EP - 392 TI - Local DNA topography correlates with functional noncoding regions of the human genome. VL - 324 SP - 389 KW - annotation KW - chromosome KW - conservation KW - dna KW - evolution KW - structure AU - Parker, Stephen AU - Hansen, Loren AU - Abaan, Hatice Ozel AU - Tullius, Thomas AU - Margulies, Elliott PY - 2009/04/17/ UR - http://dx.doi.org/10.1126/science.1169050 ER -