A systematic approach to identify functional motifs within vertebrate developmental enhancers

Qiang Li, Deborah Ritter, Nan Yang, Zhiqiang Dong, Hao Li, Jeffrey H. Chuang, Su Guo

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Uncovering the cis-regulatory logic of developmental enhancers is critical to understanding the role of non-coding DNA in development. However, it is cumbersome to identify functional motifs within enhancers, and thus few vertebrate enhancers have their core functional motifs revealed. Here we report a combined experimental and computational approach for discovering regulatory motifs in developmental enhancers. Making use of the zebrafish gene expression database, we computationally identified conserved non-coding elements (CNEs) likely to have a desired tissue-specificity based on the expression of nearby genes. Through a high throughput and robust enhancer assay, we tested the activity of ∼ 100 such CNEs and efficiently uncovered developmental enhancers with desired spatial and temporal expression patterns in the zebrafish brain. Application of de novo motif prediction algorithms on a group of forebrain enhancers identified five top-ranked motifs, all of which were experimentally validated as critical for forebrain enhancer activity. These results demonstrate a systematic approach to discover important regulatory motifs in vertebrate developmental enhancers. Moreover, this dataset provides a useful resource for further dissection of vertebrate brain development and function.

Original languageEnglish
Pages (from-to)484-495
Number of pages12
JournalDevelopmental Biology
Volume337
Issue number2
DOIs
StatePublished - 15 Jan 2010
Externally publishedYes

Keywords

  • Brain development
  • Conserved non-coding elements
  • Enhancers
  • Motifs
  • Zebrafish

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