@article {539741,
	title = {DNA-binding specificity changes in the evolution of forkhead transcription factors},
	journal = {Proc Natl Acad Sci U S A},
	volume = {110},
	number = {30},
	year = {2013},
	note = {<p>Nakagawa, SoGisselbrecht, Stephen SRogers, Julia MHartl, Daniel LBulyk, Martha LengR01 HG003985/HG/NHGRI NIH HHS/T32 GM008313/GM/NIGMS NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t2013/07/10 06:00Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12349-54. doi: 10.1073/pnas.1310430110. Epub 2013 Jul 8.</p>},
	month = {Jul 23},
	pages = {12349-54},
	abstract = {<p>The evolution of transcriptional regulatory networks entails the expansion and diversification of transcription factor (TF) families. The forkhead family of TFs, defined by a highly conserved winged helix DNA-binding domain (DBD), has diverged into dozens of subfamilies in animals, fungi, and related protists. We have used a combination of maximum-likelihood phylogenetic inference and independent, comprehensive functional assays of DNA-binding capacity to explore the evolution of DNA-binding specificity within the forkhead family. We present converging evidence that similar alternative sequence preferences have arisen repeatedly and independently in the course of forkhead evolution. The vast majority of DNA-binding specificity changes we observed are not explained by alterations in the known DNA-contacting amino acid residues conferring specificity for canonical forkhead binding sites. Intriguingly, we have found forkhead DBDs that retain the ability to bind very specifically to two completely distinct DNA sequence motifs. We propose an alternate specificity-determining mechanism whereby conformational rearrangements of the DBD broaden the spectrum of sequence motifs that a TF can recognize. DNA-binding bispecificity suggests a previously undescribed source of modularity and flexibility in gene regulation and may play an important role in the evolution of transcriptional regulatory networks.</p>},
	keywords = {*Biological Evolution, Acanthamoeba castellanii/metabolism, Amino Acid Sequence, Animals, Binding Sites, DNA/*metabolism, Forkhead Transcription Factors/chemistry/classification/*metabolism, Mice, Models, Molecular, Molecular Sequence Data, Phylogeny, Sequence Homology, Amino Acid},
	isbn = {1091-6490 (Electronic)0027-8424 (Linking)},
	author = {Nakagawa, S. and Gisselbrecht, S. S. and Rogers, J. M. and Hartl, D. L. and Bulyk, M. L.}
}
