A systematic approach to identify functional motifs within vertebrate developmental enhancers.

TitleA systematic approach to identify functional motifs within vertebrate developmental enhancers.
Publication TypeJournal Article
Year of Publication2010
AuthorsLi, Q, Ritter, D, Yang, N, Dong, Z, Li, H, Chuang, JH, Guo, S
JournalDev Biol
Volume337
Issue2
Pagination484-95
Date Published2010 Jan 15
ISSN1095-564X
KeywordsAnimals, Base Sequence, Brain, Computational Biology, Conserved Sequence, Databases, Genetic, DNA, Intergenic, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Molecular Sequence Data, Mutation, Organ Specificity, Reproducibility of Results, Time Factors, Zebrafish
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.

DOI10.1016/j.ydbio.2009.10.019
Alternate JournalDev. Biol.
PubMed ID19850031
PubMed Central IDPMC3330829
Grant ListR01 GM070808 / GM / NIGMS NIH HHS / United States
R01 NS042626-01A2 / NS / NINDS NIH HHS / United States
R01 NS042626-02 / NS / NINDS NIH HHS / United States
R21 HD051835-02 / HD / NICHD NIH HHS / United States
R01 NS042626-05 / NS / NINDS NIH HHS / United States
R01 NS042626 / NS / NINDS NIH HHS / United States
GM 70808 / GM / NIGMS NIH HHS / United States
HD 051835 / HD / NICHD NIH HHS / United States
R01 NS042626-04 / NS / NINDS NIH HHS / United States
R21 HD051835-01A1 / HD / NICHD NIH HHS / United States
NS 042626 / NS / NINDS NIH HHS / United States
R01 NS042626-03 / NS / NINDS NIH HHS / United States
R21 HD051835 / HD / NICHD NIH HHS / United States