PUBLICATION

A systematic approach to identify functional motifs within vertebrate developmental enhancers

Authors
Li, Q., Ritter, D., Yang, N., Dong, Z., Li, H., Chuang, J.H., and Guo, S.
ID
ZDB-PUB-091101-2
Date
2010
Source
Developmental Biology   337(2): 484-495 (Journal)
Registered Authors
Dong, Zhiqiang, Guo, Su, Li, Qiang, Yang, Nan
Keywords
Enhancers, Motifs, Conserved non-coding elements, Zebrafish, Brain development
MeSH Terms
  • Enhancer Elements, Genetic*
  • Computational Biology/methods*
  • Brain/embryology
  • Brain/metabolism
  • DNA, Intergenic/genetics
  • Molecular Sequence Data
  • Organ Specificity/genetics
  • Reproducibility of Results
  • Databases, Genetic
  • Time Factors
  • Gene Expression Regulation, Developmental
  • Base Sequence
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Conserved Sequence
  • Animals
  • Mutation/genetics
(all 17)
PubMed
19850031 Full text @ Dev. Biol.
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 approximately 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.
Genes / Markers
Figures
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Phenotype
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s2501TgTransgenic Insertion
    s2502TgTransgenic Insertion
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      Human Disease / Model
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      Sequence Targeting Reagents
      Fish
      Fish
      s2501Tg
      s2502Tg
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      Antibodies
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      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
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      Mapping
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      Citation
      Li, Q., Ritter, D., Yang, N., Dong, Z., Li, H., Chuang, J.H., and Guo, S. (2010) A systematic approach to identify functional motifs within vertebrate developmental enhancers. Developmental Biology. 337(2):484-495.