quantitative models of the mechanisms that control genome-wide patterns of transcription factor binding during early drosophila development量化模型的机制,控制全基因组转录因子结合在果蝇早期发展的模式.pdfVIP

Quantitative Models of the Mechanisms That Control Genome-Wide Patterns of Transcription Factor Binding during Early Drosophila Development 1 2 3 3 3 Tommy Kaplan , Xiao-Yong Li , Peter J. Sabo , Sean Thomas , John A. Stamatoyannopoulos , Mark D. Biggin4*, Michael B. Eisen1,2,4* 1 Department of Molecular and Cell Biology, California Institute of Quantitative Biosciences, University of California Berkeley, Berkeley, California, United States of America, 2 Howard Hughes Medical Institute, University of California Berkeley, Berkeley, California, United States of America, 3 Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America, 4 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America Abstract Transcription factors that drive complex patterns of gene expression during animal development bind to thousands of genomic regions, with quantitative differences in binding across bound regions mediating their activity. While we now have tools to characterize the DNA affinities of these proteins and to precisely measure their genome-wide distribution in vivo, our understanding of the forces that determine where, when, and to what extent they bind remains primitive. Here we use a thermodynamic model of transcription factor binding to evaluate the contribution of different biophysical forces to the binding of five regulators of early embryonic anterior-posterior patterning in Drosophila melanogaster. Predictions based on DNA sequence and in vitro protein-DNA affinities alone achieve a correlation of ,0.4 with experimental measurements of in vivo binding. Incorporating cooperativity and competition among the five factors, and accounting f