Genome-wide Prediction of Mammalian Enhancers Based on Analysis of Transcription-Factor Binding Affinity
Understanding the regulation of human gene expression requires knowledge of the “second genetic code,” which consists of the binding specificities of transcription factors (TFs) and the combinatorial code by which TF binding sites are assembled to form tissue-specific enhancer elements. Using a nove...
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| Veröffentlicht in: | Cell 2006-01, Vol.124 (1), p.47-59 |
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| container_title | Cell |
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| creator | Hallikas, Outi Palin, Kimmo Sinjushina, Natalia Rautiainen, Reetta Partanen, Juha Ukkonen, Esko Taipale, Jussi |
| description | Understanding the regulation of human gene expression requires knowledge of the “second genetic code,” which consists of the binding specificities of transcription factors (TFs) and the combinatorial code by which TF binding sites are assembled to form tissue-specific enhancer elements. Using a novel high-throughput method, we determined the DNA binding specificities of GLIs 1–3, Tcf4, and c-Ets1, which mediate transcriptional responses to the Hedgehog (Hh), Wnt, and Ras/MAPK signaling pathways. To identify mammalian enhancer elements regulated by these pathways on a genomic scale, we developed a computational tool, enhancer element locator (EEL). We show that EEL can be used to identify Hh and Wnt target genes and to predict activated TFs based on changes in gene expression. Predictions validated in transgenic mouse embryos revealed the presence of multiple tissue-specific enhancers in mouse c-
Myc and N-
Myc genes, which has implications for organ-specific growth control and tumor-type specificity of oncogenes. |
| doi_str_mv | 10.1016/j.cell.2005.10.042 |
| format | Article |
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| subjects | Amino Acid Sequence Animals Carrier Proteins - genetics Carrier Proteins - metabolism Chickens Computational Biology - methods Drosophila Drosophila Proteins - genetics Drosophila Proteins - metabolism Enhancer Elements, Genetic - genetics Gene Expression Regulation - physiology Genes, myc - physiology Genome Hedgehog Proteins Humans Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Mice Molecular Sequence Data Oligonucleotide Array Sequence Analysis - methods Protein Binding - physiology Rats Signal Transduction - genetics Signal Transduction - physiology Tetraodontiformes Transcription Factors - metabolism Tumor Suppressor Protein p53 - genetics Wnt Proteins - genetics Wnt Proteins - metabolism |
| title | Genome-wide Prediction of Mammalian Enhancers Based on Analysis of Transcription-Factor Binding Affinity |
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