Differences in enhancer activity in mouse and zebrafish reporter assays are often associated with changes in gene expression

Ariza-Cosano, Ana; Visel, Axel; Pennacchio, Len A.; Fraser, Hunter B.; Gómez-Skarmeta, José; Irimia, Manuel; Bessa, José

doi:10.1186/1471-2164-13-713

Differences in enhancer activity in mouse and zebrafish reporter assays are often associated with changes in gene expression

Journal Article · Wed Dec 19 00:00:00 UTC 2012 · BMC Genomics

DOI:https://doi.org/10.1186/1471-2164-13-713· OSTI ID:1626418

Ariza-Cosano, Ana ^[1]; Visel, Axel ^[2]; Pennacchio, Len A. ^[2]; Fraser, Hunter B. ^[3]; Gómez-Skarmeta, José ^[4]; Irimia, Manuel ^[5]; Bessa, José ^[4]

Universidad Pablo de Olavide-Junta de Andalucía, Seville (Spain). CSIC. Centro Andaluz de Biología del Desarrollo (CABD); DOE/OSTI
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
Stanford Univ., CA (United States). Dept. of Biology
Universidad Pablo de Olavide-Junta de Andalucía, Seville (Spain). CSIC. Centro Andaluz de Biología del Desarrollo (CABD)
Stanford Univ., CA (United States). Dept. of Biology; Univ. of Toronto, ON (Canada). The Donnelly Centre

Background: Phenotypic evolution in animals is thought to be driven in large part by differences in gene expression patterns, which can result from sequence changes in cis-regulatory elements (cis-changes) or from changes in the expression pattern or function of transcription factors (trans-changes). While isolated examples of trans-changes have been identified, the scale of their overall contribution to regulatory and phenotypic evolution remains unclear. Results: Here, we attempt to examine the prevalence of trans-effects and their potential impact on gene expression patterns in vertebrate evolution by comparing the function of identical human tissue-specific enhancer sequences in two highly divergent vertebrate model systems, mouse and zebrafish. Among 47 human conserved non-coding elements (CNEs) tested in transgenic mouse embryos and in stable zebrafish lines, at least one species-specific expression domain was observed in the majority (83%) of cases, and 36% presented dramatically different expression patterns between the two species. Although some of these discrepancies may be due to the use of different transgenesis systems in mouse and zebrafish, in some instances we found an association between differences in enhancer activity and changes in the endogenous gene expression patterns between mouse and zebrafish, suggesting a potential role for trans-changes in the evolution of gene expression. Conclusions: In total, our results: (i) serve as a cautionary tale for studies investigating the role of human enhancers in different model organisms, and (ii) suggest that changes in the trans environment may play a significant role in the evolution of gene expression in vertebrates.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1626418

Journal Information:: BMC Genomics, Journal Name: BMC Genomics Journal Issue: 1 Vol. 13; ISSN 1471-2164

Publisher:: SpringerCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Differences in enhancer activity in mouse and zebrafish reporter assays are often associated with changes in gene expression

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