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To identify these determinants, researchers have developed different methods of screening random libraries using fluorescent reporters or antibiotic resistance genes. Here, we have implemented a generic approach called ELM-seq (expression level monitoring by DNA methylation) that overcomes the technical limitations of such classic reporters. ELM-seq uses DamID (<jats:italic>Escherichia coli<\/jats:italic> DNA adenine methylase as a reporter coupled with methylation-sensitive restriction enzyme digestion and high-throughput sequencing) to enable in vivo quantitative analyses of upstream regulatory sequences. Using the genome-reduced bacterium <jats:italic>Mycoplasma pneumoniae<\/jats:italic>, we show that ELM-seq has a large dynamic range and causes minimal toxicity. We use ELM-seq to determine key sequences (known and putatively novel) of promoter and untranslated regions that influence transcription and translation efficiency. Applying ELM-seq to other organisms will help us to further understand gene expression and guide synthetic biology.<\/jats:p>","DOI":"10.1038\/s41467-017-00239-7","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T14:37:24Z","timestamp":1503412644000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["A reporter system coupled with high-throughput sequencing unveils key bacterial transcription and translation determinants"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5992-9186","authenticated-orcid":false,"given":"Eva","family":"Yus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Seong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e0","family":"Sogues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,28]]},"reference":[{"key":"239_CR1","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1007\/BF00180576","volume":"34","author":"B Surek","year":"1991","unstructured":"Surek, B., Wilhelm, M. & Hillen, W. 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