Genome-wide Prediction of Mammalian Enhancers Based on Analysis of Transcription-Factor Binding Affinity

@article{citeulike:463783, abstract = {SummaryUnderstanding 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.}, author = {Hallikas, Outi and Palin, Kimmo and Sinjushina, Natalia and Rautiainen, Reetta and Partanen, Juha and Ukkonen, Esko and Taipale, Jussi }, citeulike-article-id = {463783}, doi = {10.1016/j.cell.2005.10.042}, journal = {Cell}, keywords = {enhancer}, month = {January}, number = {1}, pages = {47--59}, posted-at = {2006-01-13 03:14:27}, priority = {2}, title = {Genome-wide Prediction of Mammalian Enhancers Based on Analysis of Transcription-Factor Binding Affinity}, url = {http://dx.doi.org/10.1016/j.cell.2005.10.042}, volume = {124}, year = {2006} }

TY - JOUR ID - citeulike:463783 L3 - citeulike-article-id:463783 TI - Genome-wide Prediction of Mammalian Enhancers Based on Analysis of Transcription-Factor Binding Affinity JF - Cell VL - 124 IS - 1 SP - 47 EP - 59 N2 - SummaryUnderstanding 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. KW - enhancer AU - Hallikas, Outi AU - Palin, Kimmo AU - Sinjushina, Natalia AU - Rautiainen, Reetta AU - Partanen, Juha AU - Ukkonen, Esko AU - Taipale, Jussi PY - 2006/01/13/ UR - http://dx.doi.org/10.1016/j.cell.2005.10.042 ER -