title: Histone acetyltransferase activity of p300 is required for the promotion of left ventricular remodeling after myocardial infarction in adult mice in vivo.
abstract: BACKGROUND
  Left ventricular (LV) remodeling after myocardial infarction is associated with hypertrophy of surviving myocytes and represents a major process that leads to heart failure. One of the intrinsic histone acetyltransferases, p300, serves as a coactivator of hypertrophy-responsive transcriptional factors such as a cardiac zinc finger protein GATA-4 and is involved in its hypertrophic stimulus-induced acetylation and DNA binding. However, the role of p300-histone acetyltransferase activity in LV remodeling after myocardial infarction in vivo is unknown.
  
  
  RESULTS
  To solve this problem, we have generated transgenic mice overexpressing intact p300 or mutant p300 in the heart. As the result of its 2-amino acid substitution in the p300-histone acetyltransferase domain, this mutant lost its histone acetyltransferase activity and was unable to activate GATA-4-dependent transcription. The two kinds of transgenic mice and the wild-type mice were subjected to myocardial infarction or sham operation at the age of 12 weeks. Intact p300 transgenic mice showed significantly more progressive LV dilation and diminished systolic function after myocardial infarction than wild-type mice, whereas mutant p300 transgenic mice did not show this.
  
  
  CONCLUSIONS
  These findings demonstrate that cardiac overexpression of p300 promotes LV remodeling after myocardial infarction in adult mice in vivo and that histone acetyltransferase activity of p300 is required for these processes.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Kawamura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morimoto
authors.forename: Koh
authors.initials: K
authors.lastname: Ono
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wada
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kawase
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumori
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Nishio
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Koji
authors.initials: K
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D050991:GATA4 Transcription Factor / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology; D051548:Histone Acetyltransferases / Q000502:physiology*; D006984:Hypertrophy / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D020257:Ventricular Remodeling; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D018797:Cell Cycle Proteins; D050991:GATA4 Transcription Factor; D051548:Histone Acetyltransferases; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor