Evolution of DNA Specificity in a Transcription Factor Family Produced a New Gene Regulatory Module
| Autor: | Eric A. Ortlund, Dave W. Anderson, Joseph W. Thornton, Michael N. Murphy, Alesia N. McKeown, Jamie T. Bridgham |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Receptors Steroid Molecular Sequence Data Cooperativity Biology Crystallography X-Ray Response Elements Article General Biochemistry Genetics and Molecular Biology DNA sequencing Evolution Molecular 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Models of DNA evolution Gene duplication Animals Humans Gene Regulatory Networks Gene Transcription factor Phylogeny 030304 developmental biology Genetics Hormone response element 0303 health sciences Biochemistry Genetics and Molecular Biology(all) chemistry 030217 neurology & neurosurgery DNA |
| Zdroj: | Cell. 159:58-68 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2014.09.003 |
| Popis: | SummaryComplex gene regulatory networks require transcription factors (TFs) to bind distinct DNA sequences. To understand how novel TF specificity evolves, we combined phylogenetic, biochemical, and biophysical approaches to interrogate how DNA recognition diversified in the steroid hormone receptor (SR) family. After duplication of the ancestral SR, three mutations in one copy radically weakened binding to the ancestral estrogen response element (ERE) and improved binding to a new set of DNA sequences (steroid response elements, SREs). They did so by establishing unfavorable interactions with ERE and abolishing unfavorable interactions with SRE; also required were numerous permissive substitutions, which nonspecifically improved cooperativity and affinity of DNA binding. Our findings indicate that negative determinants of binding play key roles in TFs’ DNA selectivity and—with our prior work on the evolution of SR ligand specificity during the same interval—show how a specific new gene regulatory module evolved without interfering with the integrity of the ancestral module. |
| Databáze: | OpenAIRE |
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