Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding.
Transcription factors (TFs) direct gene expression by binding to DNA regulatory regions. To explore the evolution of gene regulation, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) to determine experimentally the genome-wide occupancy of two TFs, CCAAT/enhancer-binding protein alpha and hepatocyte nuclear factor 4 alpha, in the livers of five vertebrates. Although each TF displays highly conserved DNA binding preferences, most binding is species-specific, and aligned binding events present in all five species are rare. Regions near genes with expression levels that are dependent on a TF are often bound by the TF in multiple species yet show no enhanced DNA sequence constraint. Binding divergence between species can be largely explained by sequence changes to the bound motifs. Among the binding events lost in one lineage, only half are recovered by another binding event within 10 kilobases. Our results reveal large interspecies differences in transcriptional regulation and provide insight into regulatory evolution.
Schmidt
Dominic
D
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Wilson
Michael D
MD
Ballester
Benoit
B
Schwalie
Petra C
PC
Brown
Gordon D
GD
Marshall
Aileen
A
Kutter
Claudia
C
Watt
Stephen
S
Martinez-Jimenez
Celia P
CP
Mackay
Sarah
S
Talianidis
Iannis
I
Flicek
Paul
P
Odom
Duncan T
DT
D000465:Algorithms; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005075:Biological Evolution; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002645:Chickens / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D016678:Genome; D015894:Genome, Human; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009893:Opossums / Q000235:genetics; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014714:Vertebrates / Q000235:genetics* / Q000378:metabolism
D022763:CCAAT-Enhancer-Binding Protein-alpha; D051557:Hepatocyte Nuclear Factor 4; D004247:DNA