Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution
| Autor: | Yuliya A. Sytnikova, Alexander Stark, Daniel Gerlach, Nelson C. Lau, Cosmas D. Arnold, Daniel Spies, Jessica Matts, Michaela Pagani |
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| Rok vydání: | 2014 |
| Předmět: |
Enhancer RNAs
Article Evolution Molecular 03 medical and health sciences 0302 clinical medicine STARR-seq Genetics Melanogaster Animals Drosophila Proteins Enhancer trap Luciferases Enhancer Cells Cultured 030304 developmental biology 0303 health sciences Genome biology Gene Expression Profiling High-Throughput Nucleotide Sequencing biology.organism_classification Enhancer Elements Genetic Drosophila Drosophila melanogaster Functional genomics 030217 neurology & neurosurgery Drosophila Protein Transcription Factors |
| Zdroj: | Nature Genetics |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.3009 |
| Popis: | Phenotypic differences between closely related species are thought to arise primarily from changes in gene expression due to mutations in cis-regulatory sequences (enhancers). However, it has remained unclear how frequently mutations alter enhancer activity or create functional enhancers de novo. Here we use STARR-seq, a recently developed quantitative enhancer assay, to determine genome-wide enhancer activity profiles for five Drosophila species in the constant trans-regulatory environment of Drosophila melanogaster S2 cells. We find that the functions of a large fraction of D. melanogaster enhancers are conserved for their orthologous sequences owing to selection and stabilizing turnover of transcription factor motifs. Moreover, hundreds of enhancers have been gained since the D. melanogaster–Drosophila yakuba split about 11 million years ago without apparent adaptive selection and can contribute to changes in gene expression in vivo. Our finding that enhancer activity is often deeply conserved and frequently gained provides functional insights into regulatory evolution. |
| Databáze: | OpenAIRE |
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