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
-
- Animals
- Base Sequence
- Brain/embryology
- Brain/metabolism
- Computational Biology/methods*
- Conserved Sequence
- DNA, Intergenic/genetics
- Databases, Genetic
- Enhancer Elements, Genetic*
- Gene Expression Regulation, Developmental
- Molecular Sequence Data
- Mutation/genetics
- Organ Specificity/genetics
- Reproducibility of Results
- Time Factors
- Zebrafish/embryology*
- Zebrafish/genetics*
- PubMed
- 19850031 Full text @ Dev. Biol.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping