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

Motif-blind, genome-wide discovery of cis-regulatory modules in Drosophila and mouse.
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DOI:
10.1016/j.devcel.2009.09.002
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发表时间:
2009-10
期刊:
影响因子:
11.8
通讯作者:
Sinha, Saurabh
Sinha, Saurabh
中科院分区:
生物学1区
文献类型:
--
作者:
Kantorovitz, Miriam R.;Kazemian, Majid;Kinston, Sarah;Miranda-Saavedra, Diego;Zhu, Qiyun;Robinson, Gene E.;Goettgens, Berthold;Halfon, Marc S.;Sinha, Saurabh

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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.
调节性DNA序列的某些统计特性及其在预测果蝇基因组中的调节区域的使用:蓬松的尾巴测试。
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