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pubmed, enhancers, article, enhancer, google, scholar, cas, melanogaster, drosophila, conserved, supplementary, nature, species, figure, sequence, central, conservation, motifs, data, functional, cell, cells, evolution, gene, transcription, yakuba, evolutionary, cisregulatory, starrseq, gained, open, number, genomic, genet, genome, access, science, similar, quantitative, factor, nat, plos, peaks, replicate, shown, regions, srp, oscs, content, show,

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nature portfolio permissions reprints privacy policy development core team european research council advertising basic research open access database social media tissue-specific cis-regulatory elements tools language tissue-specific transcriptional regulation follicle cells—gene expression transcription factor–binding profiles nature 433 nature 440 nature 474 nature 450 nature 430 nature 403 nature 416 nature 461 nature library cloning vertebrate chip-seq reveals author correspondence springerlink instant access constant trans-regulatory environment comparative chip-seq analyses permissions starr-seq identifies active gene expression due vivo gene expression genome-wide identification melanogaster–drosophila yakuba split rna-seq data gain-versus-loss ratios cis-regulatory evolution cosmas starr-seq osc enhancers trans gene regulation de novo design eukaryotic enhancer element transcription factor binding open enhancers data point represents privacy enhancer peak summits supplementary figure 1a supplementary figure 1b

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         headline:Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution
         description:Alexander Stark and colleagues use STARR-seq, a quantitative enhancer assay, to determine enhancer activity profiles for the genomes of five Drosophila species in Drosophila melanogaster S2 cells. They find that a large fraction of D. melanogaster enhancers are functionally conserved and enhancer activity is frequently gained. 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.
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      description:Alexander Stark and colleagues use STARR-seq, a quantitative enhancer assay, to determine enhancer activity profiles for the genomes of five Drosophila species in Drosophila melanogaster S2 cells. They find that a large fraction of D. melanogaster enhancers are functionally conserved and enhancer activity is frequently gained. 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.
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         Animal Genetics and Genomics
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