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Here we show that SET domain-containing 5 (Setd5) is divergently transcribed with Gt(ROSA26)Sor, is necessary for mammalian development, and interacts with the PAF1 co-transcriptional complex and other proteins. Setd5-deficient mouse embryos exhibit severe defects in neural tube formation, somitogenesis and cardiac development, have aberrant vasculogenesis in embryos, yolk sacs and placentas, and die between embryonic day 10.5 and 11.5. Setd5-deficient embryonic stem cells have impaired cellular proliferation, increased apoptosis, defective cell cycle progression, a diminished ability to differentiate into cardiomyocytes and greatly perturbed gene expression. SETD5 co-immunoprecipitates with multiple components of the PAF1 and histone deacetylase-containing NCoR complexes and is not solely required for major histone lysine methylation marks. In the absence of Setd5, histone acetylation is increased at transcription start sites and near downstream regions. These findings suggest that SETD5 functions in a manner similar to yeast Set3p and Drosophila UpSET, and that it is essential for regulating histone acetylation during gene transcription.<\/jats:p>","DOI":"10.1242\/dev.141465","type":"journal-article","created":{"date-parts":[[2016,11,18]],"date-time":"2016-11-18T21:20:36Z","timestamp":1479504036000},"page":"4595-4607","source":"Crossref","is-referenced-by-count":76,"title":["<i>Setd5<\/i>\n                    is essential for mammalian development and the co-transcriptional regulation of histone acetylation"],"prefix":"10.1242","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9513-2262","authenticated-orcid":false,"given":"Anna B.","family":"Osipovich","sequence":"first","affiliation":[{"name":"Center for Stem Cell Biology, Vanderbilt University 1 , Nashville, TN 37232 , USA"},{"name":"Vanderbilt University 2 Department of Molecular Physiology and Biophysics , , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama","family":"Gangula","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology, Vanderbilt University 1 , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro G.","family":"Vianna","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology, Vanderbilt University 1 , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8824-6499","authenticated-orcid":false,"given":"Mark A.","family":"Magnuson","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology, Vanderbilt University 1 , Nashville, TN 37232 , USA"},{"name":"Vanderbilt University 2 Department of Molecular Physiology and Biophysics , , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061213161512200_DEV141465C1","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1038\/sj.embor.7401045","article-title":"Paf1 complex homologues are required for Notch-regulated transcription during somite segmentation","volume":"8","author":"Akanuma","year":"2007","journal-title":"EMBO Rep."},{"key":"2024061213161512200_DEV141465C2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.molcel.2008.02.030","article-title":"Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control","volume":"30","author":"Bhaskara","year":"2008","journal-title":"Mol. 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