title: Critical role of YY1 in cardiac morphogenesis.
abstract: BACKGROUND
  Yin Yang 1 (YY1), the only DNA binding polycomb group protein, was reported to regulate cardiomyocyte differentiation during early cardiac mesoderm development. However, whether it contributes to cardiac morphogenesis at later developmental stage(s) during embryogenesis is unknown.
  
  
  RESULTS
  We excised YY1 in murine hearts during embryogenesis using two temporal-spatially controlled cre activation approaches, and revealed critical roles of YY1 in cardiac structural formation. Alpha-myosin heavy chain-cre (α-MHC-cre)-mediated cardiomyocyte-specific ablation of YY1 (MHC-YY1) resulted in perinatal death of mutant mice, and Nkx2.5-cre-mediated YY1 null embryos (Nkx2.5-YY1) died embryonically. In the Nkx2.5-YY1 mutants, the endocardial cushions (ECs) of both atrioventricular canal (AVC) and outflow tract (OFT) were hypoplastic due to decreased proliferation and increased apoptosis. Endothelial-to-mesenchymal transition (EMT) progress was also compromised in ECs. Nkx2.5-YY1 mutant hearts had normal formation of extracellular matrix, suggesting that the impaired EMT resulted from the direct loss of YY1. We further uncovered that a number of factors that are involved in normal cardiogenesis were downstream targets of YY1.
  
  
  CONCLUSIONS
  YY1 plays a critical role in cardiac development and occupies a high-level position within the hierarchy of the cardiac transcriptional network that governs normal cardiogenesis.
authors.affiliation: Center for Stem Cell Engineering, Department of Basic Research Laboratories, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas.
authors.forename: Ilimbek
authors.initials: I
authors.lastname: Beketaev
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Ling
authors.initials: L
authors.lastname: Qian
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology*; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D024723:Ventricular Myosins / Q000235:genetics / Q000378:metabolism; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D024723:Ventricular Myosins
keywords: Nkx2.5-cre; PcG protein; YY1; alpha-myosin heavy chain (MHC)-cre; cardiac morphogenesis