scholarly journals SP Transcription Factor Paralogs and DNA-Binding Sites Coevolve and Adaptively Converge in Mammals and Birds

2012 ◽  
Vol 4 (11) ◽  
pp. 1102-1117 ◽  
Author(s):  
Ken Daigoro Yokoyama ◽  
David D. Pollock
eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Dave W Anderson ◽  
Alesia N McKeown ◽  
Joseph W Thornton

Complexes of specifically interacting molecules, such as transcription factor proteins (TFs) and the DNA response elements (REs) they recognize, control most biological processes, but little is known concerning the functional and evolutionary effects of epistatic interactions across molecular interfaces. We experimentally characterized all combinations of genotypes in the joint protein-DNA sequence space defined by an historical transition in TF-RE specificity that occurred some 500 million years ago in the DNA-binding domain of an ancient steroid hormone receptor. We found that rampant epistasis within and between the two molecules was essential to specific TF-RE recognition and to the evolution of a novel TF-RE complex with unique derived specificity. Permissive and restrictive epistatic mutations across the TF-RE interface opened and closed potential evolutionary paths accessible by the other, making the evolution of each molecule contingent on its partner's history and allowing a molecular complex with novel specificity to evolve.


2009 ◽  
Vol 83 (17) ◽  
pp. 8893-8904 ◽  
Author(s):  
Philip Lashmit ◽  
Shuhui Wang ◽  
Hongmei Li ◽  
Hiroki Isomura ◽  
Mark F. Stinski

ABSTRACT One of the two SP1 sites in the proximal enhancer of the human cytomegalovirus (HCMV) major immediate-early (MIE) promoter is essential for transcription in human fibroblast cells (H. Isomura, M. F. Stinski, A. Kudoh, T. Daikoku, N. Shirata, and T. Tsurumi, J. Virol. 79:9597-9607, 2005). Upstream of the two SP1 sites to −223 relative to the +1 transcription start site, there are an additional five DNA binding sites for eukaryotic transcription factors. We determined the effects of the various transcription factor DNA binding sites on viral MIE RNA transcription, viral gene expression, viral DNA synthesis, or infectious virus production. We prepared recombinant HCMV bacterial artificial chromosome (BAC) DNAs with either one site missing or one site present upstream of the two SP1 sites. Infectious recombinant HCMV BAC DNAs were transfected into various cell types to avoid the effect of the virion-associated transactivators. Regardless of the cell type, which included human fibroblast, endothelial, and epithelial cells, the CREB site had the most significant and independent effect on the MIE promoter. The other sites had a minor independent effect. However, the combination of the different transcription factor DNA binding sites was significantly stronger than multiple duplications of the CREB site. These findings indicate that the CREB site in the presence of the other sites has a major role for the replication of HCMV.


Sign in / Sign up

Export Citation Format

Share Document