%0 Journal Article
%T Dramatic changes in transcription factor binding over evolutionary time
%A Matthew T Weirauch
%A Timothy R Hughes
%J Genome Biology
%D 2010
%I BioMed Central
%R 10.1186/gb-2010-11-6-122
%X It is a long standing hypothesis that alterations in transcriptional regulation are a major driving force in evolution, and the results of many recent studies offer corroborating evidence (reviewed in [1]). Recent studies also indicate that cis-regulatory sequence is the major determinant of differences in transcriptional output among related species, as opposed to other influences, such as changes in transcription factor (TF) DNA binding domains, other chromatin factors, or external signals. Wilson et al. [2] showed that mouse liver cells containing human chromosome 21 'read' the human DNA in much the same way as do human liver cells, with the TFs hepatocyte nuclear factor (HNF)1A, HNF4A, and HNF6 all binding the same chromosome 21 locations that they would in human, rather than the locations bound in the orthologous mouse chromosome. However, important details have remained elusive, including the degree to which regulatory interactions vary between species across the entire genome, the types of mutations that are responsible for regulatory changes, and whether striking differences in TF binding occupancy are observed more generally among species. In a recent issue of Science, Schmidt et al. [3] now show that individual regulatory elements are frequently gained and lost among vertebrates and that local cis-regulatory point mutations can account for much of the evolution of transcriptional regulation.In this study, the authors [3] performed chromatin immunoprecipitation sequencing (ChIP-Seq) analysis in order to determine the genomic occupancy of the strongly conserved TFs CCAAT/Enhancer binding protein ¦Á (CEBPA) and HNF4A in the liver tissues of five vertebrates (human, mouse, dog, opossum, and chicken). Both TFs are known to have important roles in liver gene regulation; in addition, liver expression patterns are mostly conserved across mammals, and liver contains a relatively small number of cell types, providing an ideal setup to compare TF occupancy in function
%U http://genomebiology.com/2010/11/6/122