Motif-Blind, Genome-Wide Discovery of cis-Regulatory Modules in Drosophila and Mouse

Miriam R. Kantorovitz, Majid Kazemian, Sarah Kinston, Diego Miranda-Saavedra, Qiyun Zhu, Gene E. Robinson, Berthold Göttgens, Marc S. Halfon, Saurabh Sinha

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)568-579
Number of pages12
JournalDevelopmental Cell
Volume17
Issue number4
DOIs
StatePublished - Oct 20 2009

Keywords

  • DEVBIO
  • DNA
  • SYSBIO

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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