Defining the sequence-recognition profile of DNA-binding molecules Export

@article{warren06, abstract = {Determining the sequence-recognition properties of DNA-binding proteins and small molecules remains a major challenge. To address this need, we have developed a high-throughput approach that provides a comprehensive profile of the binding properties of DNA-binding molecules. The approach is based on displaying every permutation of a duplex DNA sequence (up to 10 positional variants) on a microfabricated array. The entire sequence space is interrogated simultaneously, and the affinity of a DNA-binding molecule for every sequence is obtained in a rapid, unbiased, and unsupervised manner. Using this platform, we have determined the full molecular recognition profile of an engineered small molecule and a eukaryotic transcription factor. The approach also yielded unique insights into the altered sequence-recognition landscapes as a result of cooperative assembly of DNA-binding molecules in a ternary complex. Solution studies strongly corroborated the sequence preferences identified by the array analysis.}, author = {Warren, Christopher L. and Kratochvil, Natasha C. S. and Hauschild, Karl E. and Foister, Shane and Brezinski, Mary L. and Dervan, Peter B. and Phillips, George N. and Ansari, Aseem Z.}, citeulike-article-id = {1570788}, doi = {doi:10.1073/pnas.0509843102}, journal = {Proc. Natl. Acad. Sci. USA}, keywords = {chemical, genomics, ligand-dna, recognition}, month = {January}, number = {4}, pages = {867--872}, posted-at = {2007-08-16 21:27:05}, priority = {0}, title = {Defining the sequence-recognition profile of {DNA}-binding molecules}, volume = {103}, year = {2006} }

TY - JOUR ID - warren06 L3 - citeulike-article-id:1570788 N2 - Determining the sequence-recognition properties of DNA-binding proteins and small molecules remains a major challenge. To address this need, we have developed a high-throughput approach that provides a comprehensive profile of the binding properties of DNA-binding molecules. The approach is based on displaying every permutation of a duplex DNA sequence (up to 10 positional variants) on a microfabricated array. The entire sequence space is interrogated simultaneously, and the affinity of a DNA-binding molecule for every sequence is obtained in a rapid, unbiased, and unsupervised manner. Using this platform, we have determined the full molecular recognition profile of an engineered small molecule and a eukaryotic transcription factor. The approach also yielded unique insights into the altered sequence-recognition landscapes as a result of cooperative assembly of DNA-binding molecules in a ternary complex. Solution studies strongly corroborated the sequence preferences identified by the array analysis. IS - 4 JF - Proc. Natl. Acad. Sci. USA EP - 872 TI - Defining the sequence-recognition profile of {DNA}-binding molecules VL - 103 SP - 867 KW - chemical KW - genomics KW - ligand-dna KW - recognition AU - Warren, Christopher AU - Kratochvil, Natasha AU - Hauschild, Karl AU - Foister, Shane AU - Brezinski, Mary AU - Dervan, Peter AU - Phillips, George AU - Ansari, Aseem PY - 2006/January// ER -