Defining the sequence-recognition profile of DNA-binding molecules

by: Christopher L Warren, Natasha C Kratochvil, Karl E Hauschild, Shane Foister, Mary L Brezinski, Peter B Dervan, George N Phillips, Aseem Z Ansari

PNAS, Vol. 103, No. 4. (24 January 2006), pp. 867-872.

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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.

@article{citeulike:482101, 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. 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 = {482101}, doi = {10.1073/pnas.0509843102}, journal = {PNAS}, keywords = {dna-binding, microarray, molecular-biology-techniques, transcription-factors}, month = {January}, number = {4}, pages = {867--872}, posted-at = {2008-01-24 20:27:11}, priority = {4}, title = {Defining the sequence-recognition profile of DNA-binding molecules}, url = {http://dx.doi.org/10.1073/pnas.0509843102}, volume = {103}, year = {2006} }

RIS record

TY - JOUR ID - citeulike:482101 L3 - citeulike-article-id:482101 TI - Defining the sequence-recognition profile of DNA-binding molecules JF - PNAS VL - 103 IS - 4 SP - 867 EP - 872 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. KW - dna-binding KW - microarray KW - molecular-biology-techniques KW - transcription-factors 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 - 2006/01/24/ UR - http://dx.doi.org/10.1073/pnas.0509843102 ER -

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