title: Chromobox protein homolog 3 is essential for stem cell differentiation to smooth muscles in vitro and in embryonic arteriogenesis.
abstract: OBJECTIVE
  Smooth muscle cell (SMC) differentiation is a critical process during cardiovascular formation and development, but the underlying molecular mechanism remains unclear.
  
  
  RESULTS
  Here we demonstrated that chromobox protein homolog 3 (Cbx3) is crucial for SMC differentiation from stem cells and that the chromodomain and chromoshadow domain of Cbx3 are responsible for Cbx3-induced SMC differentiation. Moreover, we identified that 4 amino acids (165 to 168) within the chromoshadow domain of Cbx3 are key elements for Cbx3 interaction with Dia-1- and Cbx3-induced SMC differentiation. Mechanistically, we found that Cbx3 mediates SMC differentiation through modulating serum response factor (SRF) recruitment to the promoters of SMC genes, in which the interaction between Cbx3 and Dia-1/SRF plays a crucial role in this process. Moreover, our in vivo study demonstrated that the misexpression of Cbx3 within neural crest cells of chick embryos resulted in the death of chick embryos at early stages because of the maldevelopment of branchial arch arteries.
  
  
  CONCLUSIONS
  Our findings suggest that the interaction between Cbx3 and Dia-1/SRF is essential for SMC differentiation from stem cells and for the development of functional cardiovascular system.
authors.affiliation: Centre for Clinical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Xiao
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Luo
authors.forename: Andriani
authors.initials: A
authors.lastname: Margariti
authors.forename: Lingfang
authors.initials: L
authors.lastname: Zeng
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
authors.forename: Shu
authors.initials: S
authors.lastname: Ye
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000080865:Formins; D055785:Gene Knockdown Techniques; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000235:genetics; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D054730:Protein Interaction Domains and Motifs; D026362:Serum Response Factor / Q000378:metabolism; D014764:Viral Proteins
chemical_list: D030161:Avian Proteins; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D000080865:Formins; D026362:Serum Response Factor; D014764:Viral Proteins; C453799:Cbx3 protein, mouse; C491464:Diap1 protein, mouse; C052951:3 protein, Bacillus phage Nf