Motif-blind, genome-wide discovery of cis-regulatory modules in Drosophila and mouse. Export

@article{citeulike:6003761, abstract = {We present new approaches to cis-regulatory module (CRM) discovery in the common scenario where relevant transcription factors and/or motifs are unknown. Beginning with a small list of CRMs mediating a common gene expression pattern, we search genome-wide for CRMs with similar functionality, using new statistical scores and without requiring known motifs or accurate motif discovery. We cross-validate our predictions on 31 regulatory networks in Drosophila and through correlations with gene expression data. Five predicted modules tested using an in vivo reporter gene assay all show tissue-specific regulatory activity. We also demonstrate our methods' ability to predict mammalian tissue-specific enhancers. Finally, we predict human CRMs that regulate early blood and cardiovascular development. In vivo transgenic mouse analysis of two predicted CRMs demonstrates that both have appropriate enhancer activity. Overall, 7/7 predictions were validated successfully in vivo, demonstrating the effectiveness of our approach for insect and mammalian genomes.}, author = {Kantorovitz, Miriam R. and Kazemian, Majid and Kinston, Sarah and Miranda-Saavedra, Diego and Zhu, Qiyun and Robinson, Gene E. and G\"{o}ttgens, Berthold and Halfon, Marc S. and Sinha, Saurabh}, citeulike-article-id = {6003761}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.devcel.2009.09.002}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S1534580709003840}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19853570}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19853570}, day = {20}, doi = {10.1016/j.devcel.2009.09.002}, issn = {1878-1551}, journal = {Developmental cell}, keywords = {development, enhancer, fly, human, prediction, rodents, tf}, month = {October}, number = {4}, pages = {568--579}, posted-at = {2009-11-04 20:55:41}, priority = {2}, title = {Motif-blind, genome-wide discovery of cis-regulatory modules in Drosophila and mouse.}, url = {http://dx.doi.org/10.1016/j.devcel.2009.09.002}, volume = {17}, year = {2009} }

TY - JOUR ID - citeulike:6003761 L3 - citeulike-article-id:6003761 N2 - We present new approaches to cis-regulatory module (CRM) discovery in the common scenario where relevant transcription factors and/or motifs are unknown. Beginning with a small list of CRMs mediating a common gene expression pattern, we search genome-wide for CRMs with similar functionality, using new statistical scores and without requiring known motifs or accurate motif discovery. We cross-validate our predictions on 31 regulatory networks in Drosophila and through correlations with gene expression data. Five predicted modules tested using an in vivo reporter gene assay all show tissue-specific regulatory activity. We also demonstrate our methods' ability to predict mammalian tissue-specific enhancers. Finally, we predict human CRMs that regulate early blood and cardiovascular development. In vivo transgenic mouse analysis of two predicted CRMs demonstrates that both have appropriate enhancer activity. Overall, 7/7 predictions were validated successfully in vivo, demonstrating the effectiveness of our approach for insect and mammalian genomes. IS - 4 JF - Developmental cell SN - 1878-1551 EP - 579 TI - Motif-blind, genome-wide discovery of cis-regulatory modules in Drosophila and mouse. VL - 17 SP - 568 KW - development KW - enhancer KW - fly KW - human KW - prediction KW - rodents KW - tf AU - Kantorovitz, Miriam AU - Kazemian, Majid AU - Kinston, Sarah AU - Miranda-Saavedra, Diego AU - Zhu, Qiyun AU - Robinson, Gene AU - Göttgens, Berthold AU - Halfon, Marc AU - Sinha, Saurabh PY - 2009/10/20/ UR - http://dx.doi.org/10.1016/j.devcel.2009.09.002 ER -