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Diversity and Complexity in DNA Recognition by Transcription Factors

2009; American Association for the Advancement of Science; Volume: 324; Issue: 5935 Linguagem: Inglês

10.1126/science.1162327

1095-9203

Gwenaël Badis, Michael F. Berger, Anthony Philippakis, Shaheynoor Talukder, Andrew R. Gehrke, Savina Jaeger, Esther T. Chan, Genita Metzler, Anastasia Vedenko, Xiaoyu Chen, Hanna S. Kuznetsov, Chi-Fong Wang, David Coburn, Daniel E. Newburger, Quaid Morris, Timothy R. Hughes, Martha L. Bulyk,

RNA and protein synthesis mechanisms

Transcriptional Regulation Gets More Complicated Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. A central goal in genome biology is to identify regulatory sequences in the genome; however, few proteins' DNA binding specificities have been characterized comprehensively. Badis et al. (p. 1720 , published online 14 May) studied 104 known and predicted transcription factors (TFs), spanning 22 structural classes, in the mouse genome. While traditional models of TF binding sites are based on a single collection of highly similar DNA sequences, binding profiles were represented better by multiple motifs. Roughly half of the TFs recognized distinct primary and secondary motifs that are different from each other. At least some of these interaction modes appeared to be attributable to biophysically distinct protein conformations, adding to the complexity of transcriptional regulation.