What does it take to evolve an enhancer? A simulation-based study of factors influencing the emergence of combinatorial regulation.
Bottom Line: There is widespread interest today in understanding enhancers, which are regulatory elements typically harboring several transcription factor binding sites and mediating the combinatorial effect of transcription factors on gene expression.We found the time-to-evolve to range between 0.5 and 10 Myr, and to vary greatly with the target expression pattern, complexity of the real enhancer known to encode that pattern, and the strength of input from specific transcription factors.Our simulations also revealed that certain features of an enhancer might evolve not due to their biological function but as aids to the evolutionary process itself.
Affiliation: Department of Computer Science, University of Illinois at Urbana-Champaign.Show MeSH
Mentions: We first tested for a correlation between time-to-evolve for a target pattern and each TF’s binding site count (or estimated occupancy) in the real CRM associated with that pattern. We found that binding site content of the TF HB has a strong positive correlation with time-to-evolve estimates (Pearson CC = 0.70, P = ; fig. 3A). We also found that total binding site content of a CRM, aggregated over all six TFs, significantly positively correlates with time-to-evolve estimates (fig. 3B); however, this effect can be attributed mostly to HB site content, as indicated by a weak partial correlation coefficient (Johnson et al. 1992) with P of 0.45.
Affiliation: Department of Computer Science, University of Illinois at Urbana-Champaign.