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Here, we report that MED12 is required for normal cardiac function, such that mice with conditional cardiac-specific deletion of MED12 display progressive dilated cardiomyopathy. Loss of MED12 perturbs expression of calcium-handling genes in the heart, consequently altering calcium cycling in cardiomyocytes and disrupting cardiac electrical activity. We identified transcription factors that regulate expression of calcium-handling genes that are downregulated in the heart in the absence of MED12, and we found that MED12 localizes to transcription factor consensus sequences within calcium-handling genes. We showed that MED12 interacts with one such transcription factor, MEF2, in cardiomyocytes and that MED12 and MEF2 co-occupy promoters of calcium-handling genes. Furthermore, we demonstrated that MED12 enhances MEF2 transcriptional activity and that overexpression of both increases expression of calcium-handling genes in cardiomyocytes. Our data support a role for MED12 as a coordinator of transcription through MEF2 and other transcription factors. We conclude that MED12 is a regulator of a network of calcium-handling genes, consequently mediating contractility in the mammalian heart.<\/jats:p>","DOI":"10.1172\/jci.insight.91920","type":"journal-article","created":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T11:22:28Z","timestamp":1500463348000},"source":"Crossref","is-referenced-by-count":30,"title":["MED12 regulates a transcriptional network of calcium-handling genes in the heart"],"prefix":"10.1172","volume":"2","author":[{"given":"Kedryn K.","family":"Baskin","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Makarewich","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"DeLeon","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenduo","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Beetz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Schrewe","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda","family":"Bassel-Duby","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and"},{"name":"Hamon Center for Regenerative Science and Medicine and"},{"name":"Sen. 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