Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Dev Biol. 2010 Jan 15;337(2):484-95. doi: 10.1016/j.ydbio.2009.10.019. Epub 2009 Oct 20.

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

Author information

  • 1Department of Biopharmaceutical Sciences, Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA 94143-2811, USA. qiang.li@ucsf.edu

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.

Copyright 2009 Elsevier Inc. All rights reserved.

PMID:
19850031
[PubMed - indexed for MEDLINE]
PMCID:
PMC3330829
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk