Quantitative Models of the Mechanisms That Control Genome-Wide Patterns of Transcription Factor Binding during Early Drosophila Development

Quantitative Models of the Mechanisms That Control Genome-Wide Patterns of Transcription Factor Binding during Early Drosophila Development: "Author Summary

During early stages of development, regulatory proteins bind DNA and control the expression of nearby genes, thereby driving spatial and temporal patterns of gene expression during development. But the biochemical forces that determine where these regulatory proteins bind are poorly understood. We gathered experimental data on the activities of several key regulators of early development of the fruit fly (Drosophila melanogaster) and developed a computational method to predict where and how strongly they will bind. We find that competition, cooperativity, and other interactions among individual regulatory proteins have a limited effect on their binding, while the global accessibility of DNA to protein binding has a significant impact on the binding of all factors. Our results suggest a practical method for predicting regulatory binding by combining experimental DNA accessibility assays with computational algorithms to determine where will binding occur among the accessible regions of the genome.

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