Requirement of transcription factor NFAT in developing atrial myocardium.
Nuclear factor of activated T cell (NFAT) is a ubiquitous regulator involved in multiple biological processes. Here, we demonstrate that NFAT is temporally required in the developing atrial myocardium between embryonic day 14 and P0 (birth). Inhibition of NFAT activity by conditional expression of dominant-negative NFAT causes thinning of the atrial myocardium. The thin myocardium exhibits severe sarcomere disorganization and reduced expression of cardiac troponin-I (cTnI) and cardiac troponin-T (cTnT). Promoter analysis indicates that NFAT binds to and regulates transcription of the cTnI and the cTnT genes. Thus, regulation of cytoskeletal protein gene expression by NFAT may be important for the structural architecture of the developing atrial myocardium.
Schubert
William
W
Dept. of Molecular Pharmacology, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, NY 10461, USA.
Yang
Xiao Yong
XY
Yang
Teddy T C
TT
Factor
Stephen M
SM
Lisanti
Michael P
MP
Molkentin
Jeffery D
JD
Rincon
Mercedes
M
Chow
Chi-Wing
CW
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics; D006325:Heart Atria / Q000002:abnormalities* / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D012518:Sarcomeres / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019210:Troponin I / Q000096:biosynthesis / Q000235:genetics; D020107:Troponin T / Q000096:biosynthesis / Q000235:genetics
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D019210:Troponin I; D020107:Troponin T