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To this end, we generated the first genome-wide map of gene regulatory elements in a nonbilaterian animal, the sea anemone <jats:italic>Nematostella vectensis<\/jats:italic>. Using chromatin immunoprecipitation followed by deep sequencing of five chromatin modifications and a transcriptional cofactor, we identified over 5000 enhancers in the <jats:italic>Nematostella<\/jats:italic> genome and could validate 75% of the tested enhancers in vivo. We found that in <jats:italic>Nematostella<\/jats:italic>, but not in yeast, enhancers are characterized by the same combination of histone modifications as in bilaterians, and these enhancers preferentially target developmental regulatory genes. Surprisingly, the distribution and abundance of gene regulatory elements relative to these genes are shared between <jats:italic>Nematostella<\/jats:italic> and bilaterian model organisms. Our results suggest that complex gene regulation originated at least 600 million yr ago, predating the common ancestor of eumetazoans.<\/jats:p>","DOI":"10.1101\/gr.162529.113","type":"journal-article","created":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T03:50:52Z","timestamp":1395201052000},"page":"639-650","source":"Crossref","is-referenced-by-count":175,"title":["Evolutionary conservation of the eumetazoan gene regulatory landscape"],"prefix":"10.1101","volume":"24","author":[{"given":"Michaela","family":"Schwaiger","sequence":"first","affiliation":[]},{"given":"Anna","family":"Sch\u00f6nauer","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9 F.","family":"Rendeiro","sequence":"additional","affiliation":[]},{"given":"Carina","family":"Pribitzer","sequence":"additional","affiliation":[]},{"given":"Alexandra","family":"Schauer","sequence":"additional","affiliation":[]},{"given":"Anna F.","family":"Gilles","sequence":"additional","affiliation":[]},{"given":"Johannes B.","family":"Schinko","sequence":"additional","affiliation":[]},{"given":"Eduard","family":"Renfer","sequence":"additional","affiliation":[]},{"given":"David","family":"Fredman","sequence":"additional","affiliation":[]},{"given":"Ulrich","family":"Technau","sequence":"additional","affiliation":[]}],"member":"246","published-online":{"date-parts":[[2014,3,18]]},"reference":[{"key":"2021111811115416000_24.4.639.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232542"},{"key":"2021111811115416000_24.4.639.2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt470"},{"key":"2021111811115416000_24.4.639.3","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr174"},{"key":"2021111811115416000_24.4.639.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.009"},{"key":"2021111811115416000_24.4.639.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1098119"},{"key":"2021111811115416000_24.4.639.6","doi-asserted-by":"publisher","DOI":"10.1101\/gr.134833.111"},{"key":"2021111811115416000_24.4.639.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2008.09.005"},{"key":"2021111811115416000_24.4.639.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1064"},{"key":"2021111811115416000_24.4.639.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.01.038"},{"key":"2021111811115416000_24.4.639.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.030"},{"key":"2021111811115416000_24.4.639.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.1182213"},{"key":"2021111811115416000_24.4.639.12","doi-asserted-by":"publisher","DOI":"10.1101\/gr.153668.112"},{"key":"2021111811115416000_24.4.639.13","doi-asserted-by":"publisher","DOI":"10.1038\/nature04863"},{"key":"2021111811115416000_24.4.639.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016071107"},{"key":"2021111811115416000_24.4.639.15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000384"},{"key":"2021111811115416000_24.4.639.16","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"2021111811115416000_24.4.639.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14863"},{"key":"2021111811115416000_24.4.639.18","doi-asserted-by":"publisher","DOI":"10.1038\/nature11247"},{"key":"2021111811115416000_24.4.639.19","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1906"},{"key":"2021111811115416000_24.4.639.20","doi-asserted-by":"publisher","DOI":"10.1101\/gr.136507.111"},{"key":"2021111811115416000_24.4.639.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002720107"},{"key":"2021111811115416000_24.4.639.22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1091946"},{"key":"2021111811115416000_24.4.639.23","first-page":"598","article-title":"Morphological evolution caused by many subtle-effect substitutions in regulatory DNA","volume":"474","year":"2012","journal-title":"Nature"},{"key":"2021111811115416000_24.4.639.24","doi-asserted-by":"publisher","DOI":"10.1007\/s00427-002-0214-7"},{"key":"2021111811115416000_24.4.639.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.08.014"},{"key":"2021111811115416000_24.4.639.26","doi-asserted-by":"crossref","unstructured":"Genikhovich G , Technau U . 2009. In situ hybridization of starlet sea anemone (Nematostella vectensis) embryos, larvae, and polyps. Cold Spring Harb Protoc doi: 10.1101\/pdb.prot5281.","DOI":"10.1101\/pdb.prot5282"},{"key":"2021111811115416000_24.4.639.27","doi-asserted-by":"publisher","DOI":"10.1126\/science.1196914"},{"key":"2021111811115416000_24.4.639.28","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts028"},{"key":"2021111811115416000_24.4.639.29","doi-asserted-by":"crossref","unstructured":"Heger P , Marin B , Bartkuhn M , Schierenberg E , Wiehe T . 2012. 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