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.
Requirement of transcription factor NFAT in developing atrial myocardium
Abbreviations used in this paper: ΔCn, constitutive active calcineurin; CsA, cyclosporin A; cTnI, cardiac troponin-I; cTnT, cardiac troponin-T; dnNFAT, dominant-negative NFAT; Dox, doxycycline; E, embryonic day; IL, interleukin; NFAT, nuclear factor of activated T cell; PPARγ2, peroxisome proliferator–activated receptor γ2; ssTnI, slow skeletal troponin-I; ssTnT, slow skeletal troponin-T; Tg+, transgenic positive; Wt, wild type.
William Schubert, Xiao Yong Yang, Teddy T.C. Yang, Stephen M. Factor, Michael P. Lisanti, Jeffery D. Molkentin, Mercedes Rincón, Chi-Wing Chow; Requirement of transcription factor NFAT in developing atrial myocardium . J Cell Biol 9 June 2003; 161 (5): 861–874. doi: https://doi.org/10.1083/jcb.200301058
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