title: Atrial identity is determined by a COUP-TFII regulatory network.
abstract: Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, the factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP-TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T tubules. Changes in atrial characteristics are accompanied by alterations of 2,584 genes, of which 81% were differentially expressed between atria and ventricles, suggesting that a major function of myocardial COUP-TFII is to determine atrial identity. Chromatin immunoprecipitation assays using E13.5 atria identified classic atrial-ventricular identity genes Tbx5, Hey2, Irx4, MLC2v, MLC2a, and MLC1a, among many other cardiac genes, as potential COUP-TFII direct targets. Collectively, our results reveal that COUP-TFII confers atrial identity through direct binding and by modulating expression of a broad spectrum of genes that have an impact on atrial development and function.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: San-pin
authors.initials: SP
authors.lastname: Wu
authors.forename: Chiang-Min
authors.initials: CM
authors.lastname: Cheng
authors.forename: Rainer B
authors.initials: RB
authors.lastname: Lanz
authors.forename: Tiannan
authors.initials: T
authors.lastname: Wang
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Respress
authors.forename: Sameer
authors.initials: S
authors.lastname: Ather
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Shaw-Jenq
authors.initials: SJ
authors.lastname: Tsai
authors.forename: Xander H T
authors.initials: XH
authors.lastname: Wehrens
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Tsai
mesh_terms: D000200:Action Potentials; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D048429:Cell Size; D047369:Chromatin Immunoprecipitation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006325:Heart Atria / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D025521:Tumor Suppressor Proteins; C511143:Bcl11b protein, mouse; C485778:Hey2 protein, mouse; C485534:Irx4 protein, mouse; C103172:T-box transcription factor 5