RT Journal
A1 Wong, Emily S.
A1 Thybert, David
A1 Schmitt, Bianca M.
A1 Stefflova, Klara
A1 Odom, Duncan T.
A1 Flicek, Paul
T1 Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
JF Genome Research 
JO Genome Research 
YR 2015 
FD February 01 
VO 25 
IS 2 
SP 167 
OP 178 
DO 10.1101/gr.177840.114 
UL http://genome.cshlp.org/content/25/2/167.abstract 
AB To understand the evolutionary dynamics between transcription factor (TF) binding and gene expression in mammals, we compared transcriptional output and the binding intensities for three tissue-specific TFs in livers from four closely related mouse species. For each transcription factor, TF-dependent genes and the TF binding sites most likely to influence mRNA expression were identified by comparing mRNA expression levels between wild-type and TF knockout mice. Independent evolution was observed genome-wide between the rate of change in TF binding and the rate of change in mRNA expression across taxa, with the exception of a small number of TF-dependent genes. We also found that binding intensities are preferentially conserved near genes whose expression is dependent on the TF, and the conservation is shared among binding peaks in close proximity to each other near the TSS. Expression of TF-dependent genes typically showed an increased sensitivity to changes in binding levels as measured by mRNA abundance. Taken together, these results highlight a significant tolerance to evolutionary changes in TF binding intensity in mammalian transcriptional networks and suggest that some TF-dependent genes may be largely regulated by a single TF across evolution.