title: Regulation of cardiomyocyte polyploidy and multinucleation by CyclinG1.
abstract: BACKGROUND
  Polyploidy and multinucleation are characteristic features of mammalian cardiomyocytes, which develop shortly after birth when most differentiated cardiomyocytes become acytokinetic. Cardiac overload and hypertrophy further increase the degree of polyploidy of cardiomyocytes, suggesting a role in cell type-specific responses to physiological and pathological stimuli.
  
  
  OBJECTIVE
  We sought to study the function of cyclinG1 in the regulation of polyploidy and multinucleation in cardiomyocytes.
  
  
  RESULTS
  We found that expression of cyclinG1, a transcriptional target of p53, coincides with arrest of cardiomyocyte proliferation and onset of polyploidization. Overexpression of cyclinG1 promoted DNA synthesis but inhibited cytokinesis in neonatal cardiomyocytes leading to an enlarged population of binuclear cardiomyocytes. Reciprocally, inactivation of the cyclinG1 gene in mice lowered the degree of polyploidy and multinucleation in cardiomyocytes. Moreover, lack of cyclinG1 prevented the increase of polynucleated cardiomyocytes in response to pressure overload and hypertrophy.
  
  
  CONCLUSIONS
  CyclinG1 is an important player for the regulation of polyploidy and multinucleation in cardiomyocytes probably by inhibition of apoptosis caused by checkpoint activation.
authors.affiliation: Max-Planck-Institut for Heart und Lung Research, D-61231 Bad Nauheim, Germany.
authors.forename: Zhipei
authors.initials: Z
authors.lastname: Liu
authors.forename: Shijing
authors.initials: S
authors.lastname: Yue
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Chen
authors.forename: Thomas
authors.initials: T
authors.lastname: Kubin
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D056766:Cyclin G1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D011123:Polyploidy; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C534703:Ccng1 protein, mouse; D056766:Cyclin G1