Automated high-throughput mapping of promoter-enhancer interactions in zebrafish embryos

Jochen Gehrig, Markus Reischl, Eva Kalmar, Marco Ferg, Yavor Hadzhiev, Andreas Zaucker, Chengyi Song, Simone Schindler, Urban Liebel, Ferenc Müller

Research output: Contribution to journalArticleScientificpeer-review

80 Citations (Scopus)

Abstract

Zebrafish embryos offer a unique combination of high-throughput capabilities and the complexity of the vertebrate animal for a variety of phenotypic screening applications. However, there is a need for automation of imaging technologies to exploit the potential of the transparent embryo. Here we report a high-throughput pipeline for registering domain-specific reporter expression in zebrafish embryos with the aim of mapping the interactions between cis-regulatory modules and core promoters. Automated microscopy coupled with custom-built embryo detection and segmentation software allowed the spatial registration of reporter activity for 202 enhancer-promoter combinations, based on images of thousands of embryos. The diversity of promoter-enhancer interaction specificities underscores the importance of the core promoter sequence in cis-regulatory interactions and provides a promoter resource for transgenic reporter studies. The technology described here is also suitable for the spatial analysis of fluorescence readouts in genetic, pharmaceutical or toxicological screens.

Original languageEnglish
Pages (from-to)911-916
JournalNature Methods
Volume6
Issue number12
DOIs
Publication statusPublished - 2009
Externally publishedYes

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