{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:08:24Z","timestamp":1791922104908,"version":"4.3.4"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,3,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">An increase in serum cortisol has been identified as a risk factor for cardiac failure, which highlights the impact of glucocorticoid signaling in cardiomyocytes and its influence in the progression of failure. Dexamethasone, a synthetic glucocorticoid, is sufficient for induction of cardiomyocyte hypertrophy, but little is known of the glucocorticoid receptor (GR) genome\u2010binding and \u2010dependent transcriptional changes that mediate this phenotype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">In this study using high\u2010resolution sequencing, we identified genomic targets of GR and associated change in the transcriptome after 1 and 24\u00a0hours of dexamethasone treatment. We showed that GR associates with 6482 genes in the cardiac genome, with differential regulation of 738 genes. Interestingly, alignment of the chromatin immunoprecipitation and RNA sequencing data show that, after 1\u00a0hour, 69% of differentially regulated genes are associated with GR and identify as regulators of RNA pol II\u2013dependent transcription. Conversely, after 24\u00a0hours only 45% of regulated genes are associated with GR and involved in dilated and hypertrophic cardiomyopathies as well as other growth\u2010related pathways. In addition, our data also reveal that a majority of genes (76.42%) associated with GR show incremental changes in transcript abundance and are genes involved in basic cellular processes that might be regulated by the dynamics of promoter\u2010paused RNA pol II, as seen in hearts undergoing hypertrophy. In vivo administration of dexamethasone resulted in similar changes in the cardiac transcriptome, as seen in isolated cardiomyocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our data reveal genome\u2010wide GR binding sites in cardiomyocytes, identify novel targets and GR\u2010dependent change in the transcriptome that induces and contributes to cardiomyocyte hypertrophy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.011484","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T09:00:28Z","timestamp":1552554028000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Glucocorticoid Receptor\u2010Binding and Transcriptome Signature in Cardiomyocytes"],"prefix":"10.1161","volume":"8","author":[{"given":"Elena","family":"Severinova","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers New Jersey Medical School Newark NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleena","family":"Alikunju","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers New Jersey Medical School Newark NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers New Jersey Medical School Newark NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puneet","family":"Dhawan","sequence":"additional","affiliation":[{"name":"Genomics Center Department of Microbiology Biochemistry and Molecular Genetics Rutgers New Jersey Medical School Newark NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazish","family":"Sayed","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute Stanford University Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danish","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers New Jersey Medical School Newark NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-5-1-25"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1530\/JME-15-0318"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.48.1.231"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-29717-0_5"},{"key":"e_1_3_2_6_2","first-page":"306","article-title":"Steroid receptor interactions with heat shock protein and immunophilin chaperones","volume":"18","author":"Pratt WB","year":"1997","unstructured":"Pratt WB, Toft DO. 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