Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner.
YY1 can activate or repress transcription of various genes. In cardiac myocytes in culture YY1 has been shown to regulate expression of several genes involved in myocyte pathology. YY1 can also acutely protect the heart against detrimental changes in gene expression. In this study we show that cardiac over-expression of YY1 induces pathologic cardiac hypertrophy in male mice, measured by changes in gene expression and lower ejection fraction/fractional shortening. In contrast, female animals are protected against pathologic gene expression changes and cardiac dysfunction. Furthermore, we show that YY1 regulates, in a sex-specific manner, the expression of mammalian enable (Mena), a factor that regulates cytoskeletal actin dynamics and whose expression is increased in several models of cardiac pathology, and that Mena expression in humans with heart failure is sex-dependent. Finally, we show that sex differences in YY1 expression are also observed in human heart failure. In summary, this is the first work to show that YY1 has a sex-specific effect in the regulation of cardiac pathology.
Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA; Division of Cardiology, Denver Health and Hospital Authority, Denver, CO, USA.
Brian L
BL
Stauffer
Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
Karen
K
Dockstader
Pontificia Universidad Católica Madre y Maestra, Departamento de Medicina, Santiago, Dominican Republic.
Gloria
G
Russell
Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
Jamie
J
Hijmans
Amherst College, USA.
Lisa
L
Walker
University of Colorado, Boulder, USA.
Mackenzie
M
Cecil
Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
Kimberly
K
Demos-Davies
Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
Allen
A
Medway
Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
Timothy A
TA
McKinsey
Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: kika.sucharov@ucdenver.edu.
Carmen C
CC
Sucharov
D000328:Adult; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D024061:Collagen Type III / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D015854:Up-Regulation; D050986:YY1 Transcription Factor / Q000235:genetics*
D024061:Collagen Type III; D003598:Cytoskeletal Proteins; C511939:Enah protein, human; C102176:Enah protein, mouse; D008840:Microfilament Proteins; D012333:RNA, Messenger; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C494699:Yy1 protein, mouse
Cardiac pathology; Fetal gene program; Heart failure; Hypertrophy; YY1