title: Steroid receptor coactivator-2 is a dual regulator of cardiac transcription factor function.
abstract: We have previously demonstrated the potential role of steroid receptor coactivator-2 (SRC-2) as a co-regulator in the transcription of critical molecules modulating cardiac function and metabolism in normal and stressed hearts. The present study seeks to extend the previous information by demonstrating SRC-2 fulfills this role by serving as a critical coactivator for the transcription and activity of critical transcription factors known to control cardiac growth and metabolism as well as in their downstream signaling. This knowledge broadens our understanding of the mechanism by which SRC-2 acts in normal and stressed hearts and allows further investigation of the transcriptional modifications mediating different types and degrees of cardiac stress. Moreover, the genetic manipulation of SRC-2 in this study is specific for the heart and thereby eliminating potential indirect effects of SRC-2 deletion in other organs. We have shown that SRC-2 is critical to transcriptional control modulated by MEF2, GATA-4, and Tbx5, thereby enhancing gene expression associated with cardiac growth. Additionally, we describe SRC-2 as a novel regulator of PPARα expression, thus controlling critical steps in metabolic gene expression. We conclude that through regulation of cardiac transcription factor expression and activity, SRC-2 is a critical transcriptional regulator of genes important for cardiac growth, structure, and metabolism, three of the main pathways altered during the cardiac stress response.
authors.affiliation: From the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Reineke
authors.affiliation: the Stem Cell Engineering Department, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas 77030.
authors.forename: Ashley
authors.initials: A
authors.lastname: Benham
authors.affiliation: the Stem Cell Engineering Department, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas 77030.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Soibam
authors.affiliation: From the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Erin
authors.initials: E
authors.lastname: Stashi
authors.affiliation: the Department of Internal Medicine, Division of Cardiology, The University of Texas Medical School at Houston, Houston, Texas 77030.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Taegtmeyer
authors.affiliation: the Department of Medicine, Division of Cardiovascular Sciences, Baylor College of Medicine, Houston, Texas 77030, and.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Entman
authors.affiliation: the Stem Cell Engineering Department, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas 77030, the Department of Biology and Biochemistry, University of Houston, Houston, Texas 77004.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
authors.affiliation: From the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, berto@bcm.tmc.edu.
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D051958:Nuclear Receptor Coactivator 2; D014157:Transcription Factors
keywords: Cardiac Metabolism; Gene Regulation; Transcription Factor; Transcription Target Gene; Transcriptional Coactivator