Detailed map of a cis-regulatory input function.

@article{citeulike:265775, abstract = {Most genes are regulated by multiple transcription factors that bind specific sites in DNA regulatory regions. These cis-regulatory regions perform a computation: the rate of transcription is a function of the active concentrations of each of the input transcription factors. Here, we used accurate gene expression measurements from living cell cultures, bearing GFP reporters, to map in detail the input function of the classic lacZYA operon of Escherichia coli, as a function of about a hundred combinations of its two inducers, cAMP and isopropyl beta-d-thiogalactoside (IPTG). We found an unexpectedly intricate function with four plateau levels and four thresholds. This result compares well with a mathematical model of the binding of the regulatory proteins cAMP receptor protein (CRP) and LacI to the lac regulatory region. The model is also used to demonstrate that with few mutations, the same region could encode much purer AND-like or even OR-like functions. This possibility means that the wild-type region is selected to perform an elaborate computation in setting the transcription rate. The present approach can be generally used to map the input functions of other genes.}, address = {Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.}, author = {Setty, Y. and Mayo, A. E. and Surette, M. G. and Alon, U. }, citeulike-article-id = {265775}, doi = {http://dx.doi.org/10.1073/pnas.1230759100}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {activation, activator, architecture, coli, combinatorial, crp, gfp, lac, model, polymerase, prokaryote, promoter, repression, repressor}, month = {June}, number = {13}, pages = {7702--7707}, posted-at = {2007-06-08 22:17:40}, priority = {0}, title = {Detailed map of a cis-regulatory input function.}, url = {http://dx.doi.org/10.1073/pnas.1230759100}, volume = {100}, year = {2003} }

TY - JOUR ID - citeulike:265775 L3 - citeulike-article-id:265775 TI - Detailed map of a cis-regulatory input function. JF - Proc Natl Acad Sci U S A VL - 100 IS - 13 SP - 7702 EP - 7707 AD - Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel. SN - 0027-8424 N2 - Most genes are regulated by multiple transcription factors that bind specific sites in DNA regulatory regions. These cis-regulatory regions perform a computation: the rate of transcription is a function of the active concentrations of each of the input transcription factors. Here, we used accurate gene expression measurements from living cell cultures, bearing GFP reporters, to map in detail the input function of the classic lacZYA operon of Escherichia coli, as a function of about a hundred combinations of its two inducers, cAMP and isopropyl beta-d-thiogalactoside (IPTG). We found an unexpectedly intricate function with four plateau levels and four thresholds. This result compares well with a mathematical model of the binding of the regulatory proteins cAMP receptor protein (CRP) and LacI to the lac regulatory region. The model is also used to demonstrate that with few mutations, the same region could encode much purer AND-like or even OR-like functions. This possibility means that the wild-type region is selected to perform an elaborate computation in setting the transcription rate. The present approach can be generally used to map the input functions of other genes. KW - activation KW - activator KW - architecture KW - coli KW - combinatorial KW - crp KW - gfp KW - lac KW - model KW - polymerase KW - prokaryote KW - promoter KW - repression KW - repressor AU - Setty, Y AU - Mayo, AE AU - Surette, MG AU - Alon, U PY - 2003/06/24/ UR - http://dx.doi.org/10.1073/pnas.1230759100 ER -