High-throughput functional comparison of promoter and enhancer activities.
Promoters initiate RNA synthesis, and enhancers stimulate promoter activity. Whether promoter and enhancer activities are encoded distinctly in DNA sequences is unknown. We measured the enhancer and promoter activities of thousands of DNA fragments transduced into mouse neurons. We focused on genomic loci bound by the neuronal activity-regulated coactivator CREBBP, and we measured enhancer and promoter activities both before and after neuronal activation. We find that the same sequences typically encode both enhancer and promoter activities. However, gene promoters generate more promoter activity than distal enhancers, despite generating similar enhancer activity. Surprisingly, the greater promoter activity of gene promoters is not due to conventional core promoter elements or splicing signals. Instead, we find that particular transcription factor binding motifs are intrinsically biased toward the generation of promoter activity, whereas others are not. Although the specific biases we observe may be dependent on experimental or cellular context, our results suggest that gene promoters are distinguished from distal enhancers by specific complements of transcriptional activators.
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
Thomas A
TA
Nguyen
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
Richard D
RD
Jones
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
Andrew R
AR
Snavely
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
Andreas R
AR
Pfenning
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA;
Rory
R
Kirchner
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom.
Martin
M
Hemberg
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
Jesse M
JM
Gray
D000818:Animals; D001665:Binding Sites; D050882:CREB-Binding Protein / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic; D051379:Mice; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
D002843:Chromatin; D004268:DNA-Binding Proteins; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse