RT Journal
A1 Verfaillie, Annelien
A1 Svetlichnyy, Dmitry
A1 Imrichova, Hana
A1 Davie, Kristofer
A1 Fiers, Mark
A1 Kalender Atak, Zeynep
A1 Hulselmans, Gert
A1 Christiaens, Valerie
A1 Aerts, Stein
T1 Multiplex enhancer-reporter assays uncover unsophisticated TP53 enhancer logic
JF Genome Research 
JO Genome Research 
YR 2016 
FD July 01 
VO 26 
IS 7 
SP 882 
OP 895 
DO 10.1101/gr.204149.116 
UL http://genome.cshlp.org/content/26/7/882.abstract 
AB Transcription factors regulate their target genes by binding to regulatory regions in the genome. Although the binding preferences of TP53 are known, it remains unclear what distinguishes functional enhancers from nonfunctional binding. In addition, the genome is scattered with recognition sequences that remain unoccupied. Using two complementary techniques of multiplex enhancer-reporter assays, we discovered that functional enhancers could be discriminated from nonfunctional binding events by the occurrence of a single TP53 canonical motif. By combining machine learning with a meta-analysis of TP53 ChIP-seq data sets, we identified a core set of more than 1000 responsive enhancers in the human genome. This TP53 cistrome is invariably used between cell types and experimental conditions, whereas differences among experiments can be attributed to indirect nonfunctional binding events. Our data suggest that TP53 enhancers represent a class of unsophisticated cell-autonomous enhancers containing a single TP53 binding site, distinct from complex developmental enhancers that integrate signals from multiple transcription factors.