کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2177389 1094644 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Motif-Blind, Genome-Wide Discovery of cis-Regulatory Modules in Drosophila and Mouse
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Motif-Blind, Genome-Wide Discovery of cis-Regulatory Modules in Drosophila and Mouse
چکیده انگلیسی

SummaryWe 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 17, Issue 4, 20 October 2009, Pages 568–579
نویسندگان
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