DOI: 10.1126/science.1131007. A Systems Approach to Measuring the Binding Energy Landscapes of Transcription Factors

A Systems Approach to Measuring the Binding Energy Landscapes of Transcription Factors

10.1126/science.1131007

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

A major goal of systems biology is to predict the function of biological networks. Although network topologies have been successfully determined in many cases, the quantitative parameters governing these networks generally have not. Measuring affinities of molecular interactions in high-throughput format remains problematic, especially for transient and low-affinity interactions. We describe a high-throughput microfluidic platform that measures such properties on the basis of mechanical trapping of molecular interactions. With this platform we characterized DNA binding energy landscapes for four eukaryotic transcription factors; these landscapes were used to test basic assumptions about transcription factor binding and to predict their in vivo function.

Bibliography

Maerkl, S. J., & Quake, S. R. (2007). A Systems Approach to Measuring the Binding Energy Landscapes of Transcription Factors. Science, 315(5809), 233â237.

Authors 2

Sebastian J. Maerkl (first)
Stephen R. Quake (additional)

References 38 Referenced 513

10.1038/nature01644
10.1126/science.1084337
10.1038/nature03441
10.1038/415141a
10.1038/415180a
10.1038/35001009
10.1038/nature02800
10.1126/science.1122088
10.1038/35002125
10.1371/journal.pbio.0040045
10.1038/nature04177
10.1073/pnas.0509843102
10.1038/ng1473
10.1073/pnas.111163698
10.1016/0092-8674(94)90318-2
10.1128/MCB.20.2.429-440.2000
10.1101/gad.1095203
10.1073/pnas.211195798
10.1091/mbc.11.12.4309
10.1074/jbc.M403818200
10.1016/0092-8674(90)90525-J
R. E. Baker, D. C. Masison, Mol. Cell. Biol.10, 2458 (1990). / Mol. Cell. Biol. (1990)
10.1006/jmbi.2002.5440
10.1016/j.bbagen.2003.12.007
10.1126/science.1076996
Materials and methods are available on Science Online.
10.1126/science.288.5463.113
10.1126/science.270.5235.467
10.1038/363038a0
10.1093/emboj/16.15.4689
10.1093/nar/30.5.1255
10.1093/nar/29.12.2471
10.1093/nar/gkf578
10.1093/nar/gkf669
10.1186/gb-2005-6-2-r18
10.1186/gb-2005-6-10-r87
10.1101/gr.1271603
We thank B. Wold and J. Berger for helpful discussions and K. Kapur and C. Jacobs for help with the document. Supported in part by Defense Advanced Research Projects Agency–Biological Input Output Systems an NIH Director's Pioneer Award and Howard Hughes Medical Institute. S.R.Q. holds equity in is a paid consultant for and is a co-founder and former director of Fluidigm which may license the device described in this paper.

Dates

Type	When
Created	18 years, 7 months ago (Jan. 12, 2007, 7:48 a.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 4:37 a.m.)
Indexed	1 day, 9 hours ago (Sept. 3, 2025, 7:06 a.m.)
Issued	18 years, 7 months ago (Jan. 12, 2007)
Published	18 years, 7 months ago (Jan. 12, 2007)
Published Print	18 years, 7 months ago (Jan. 12, 2007)

Funders 0

None

BibTeX

@article{Maerkl_2007, title={A Systems Approach to Measuring the Binding Energy Landscapes of Transcription Factors}, volume={315}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1131007}, DOI={10.1126/science.1131007}, number={5809}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Maerkl, Sebastian J. and Quake, Stephen R.}, year={2007}, month=jan, pages={233–237} }

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