title: cis-Regulatory control of Mesp1 expression by YY1 and SP1 during mouse embryogenesis.
abstract: BACKGROUND
  Mesp1 is critical for early cardiomyocyte differentiation and heart development. We previously observed down-regulation of Mesp1 expression in YY1-ablated mouse embryonic hearts. However, how Mesp1 expression is mediated by YY1 is not well understood.
  
  
  RESULTS
  We excised YY1 in the murine embryos using Sox2-cre and found that Mesp1 was down-regulated in the embryonic day (E) 7.5 mutant embryos. Also, YY1 activated the 6 kb Mesp1 regulatory element fused to a luciferase reporter. We identified two putative YY1 binding sites in the proximal promoter region of Mesp1 gene, and found that mutation of these sites significantly reduced YY1-induced activation of the Mesp1 promoter. We also uncovered one cognitive site for SP1, one of the earliest binding partners of YY1 identified. Mutation of this SP1 site repressed SP1-induced activation of the Mesp1 promoter. Moreover, YY1 and SP1 synergistically activated the Mesp1 promoter. Consistently, while Lacz expression driven by the wild-type 6 kb regulatory element of Mesp1 gene was robust in E7.5 mouse embryos, the mutation of these binding sites in the context of this 6 kb sequence substantially reduced the LacZ expression during embryogenesis.
  
  
  CONCLUSIONS
  YY1 and SP1 independently and cooperatively govern the Mesp1 expression during embryogenesis.
authors.affiliation: Center for Stem Cell Engineering, Department of Basic Research Laboratories, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, USA.
authors.forename: Ilimbek
authors.initials: I
authors.lastname: Beketaev
authors.affiliation: In Vitro Fertilization Center, Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
authors.forename: Kuo-Chan
authors.initials: KC
authors.lastname: Weng
authors.affiliation: Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, Massachusetts, USA.
authors.forename: Siyeon
authors.initials: S
authors.lastname: Rhee
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, Massachusetts, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Mager
authors.affiliation: Center for Stem Cell Engineering, Department of Basic Research Laboratories, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D004622:Embryo, Mammalian / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D051379:Mice; D038081:Organogenesis / Q000502:physiology*; D020218:Response Elements / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016329:Sp1 Transcription Factor; D050986:YY1 Transcription Factor; C101538:Mesp1 protein, mouse; C494699:Yy1 protein, mouse
keywords: Mesp1; SP1; YY1; embryogenesis