Requirement of Transcription Factor NFAT in Developing Atrial Myocardium

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2003 Jun 11

PMID 12796475

Citations 13

Authors

William Schubert

Xiao Yong Yang

Teddy T C Yang

Stephen M Factor

Michael P Lisanti

Jeffery D Molkentin

Mercedes Rincon

Chi-Wing Chow

Affiliations

Soon will be listed here.

Abstract

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.

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References

Musaro A, McCullagh K, Naya F, Olson E, Rosenthal N . IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1. Nature. 1999; 400(6744):581-5. DOI: 10.1038/23060. View

Graef I, Chen F, Chen L, Kuo A, Crabtree G . Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature. Cell. 2001; 105(7):863-75. DOI: 10.1016/s0092-8674(01)00396-8. View

Ren D, Collingwood T, Rebar E, Wolffe A, Camp H . PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. Genes Dev. 2002; 16(1):27-32. PMC: 155307. DOI: 10.1101/gad.953802. View

Sugden P . Signalling pathways in cardiac myocyte hypertrophy. Ann Med. 2002; 33(9):611-22. View

Ohno-Matsui K, Hirose A, Yamamoto S, Saikia J, Okamoto N, Gehlbach P . Inducible expression of vascular endothelial growth factor in adult mice causes severe proliferative retinopathy and retinal detachment. Am J Pathol. 2002; 160(2):711-9. PMC: 1850637. DOI: 10.1016/S0002-9440(10)64891-2. View

Perl A, Tichelaar J, Whitsett J . Conditional gene expression in the respiratory epithelium of the mouse. Transgenic Res. 2002; 11(1):21-9. DOI: 10.1023/a:1013986627504. View

Gunther E, Belka G, Wertheim G, Wang J, Hartman J, Boxer R . A novel doxycycline-inducible system for the transgenic analysis of mammary gland biology. FASEB J. 2002; 16(3):283-92. DOI: 10.1096/fj.01-0551com. View

Horsley V, Pavlath G . NFAT: ubiquitous regulator of cell differentiation and adaptation. J Cell Biol. 2002; 156(5):771-4. PMC: 2173310. DOI: 10.1083/jcb.200111073. View

Turner A, Hooper N . The angiotensin-converting enzyme gene family: genomics and pharmacology. Trends Pharmacol Sci. 2002; 23(4):177-83. DOI: 10.1016/s0165-6147(00)01994-5. View

10.

Yang T, Xiong Q, Enslen H, Davis R, Chow C . Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases. Mol Cell Biol. 2002; 22(11):3892-904. PMC: 133816. DOI: 10.1128/MCB.22.11.3892-3904.2002. View

11.

Saneyoshi T, Kume S, Amasaki Y, Mikoshiba K . The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature. 2002; 417(6886):295-9. DOI: 10.1038/417295a. View

12.

A Crackower M, Sarao R, Oudit G, Yagil C, Kozieradzki I, Scanga S . Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002; 417(6891):822-8. DOI: 10.1038/nature00786. View

13.

Eriksson U, Danilczyk U, Penninger J . Just the beginning: novel functions for angiotensin-converting enzymes. Curr Biol. 2002; 12(21):R745-52. DOI: 10.1016/s0960-9822(02)01255-1. View

14.

Frey N, Olson E . Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol. 2003; 65:45-79. DOI: 10.1146/annurev.physiol.65.092101.142243. View

15.

Yang T, Chow C . Transcription cooperation by NFAT.C/EBP composite enhancer complex. J Biol Chem. 2003; 278(18):15874-85. DOI: 10.1074/jbc.M211560200. View

16.

Durand D, Shaw J, Bush M, Replogle R, Belagaje R, Crabtree G . Characterization of antigen receptor response elements within the interleukin-2 enhancer. Mol Cell Biol. 1988; 8(4):1715-24. PMC: 363332. DOI: 10.1128/mcb.8.4.1715-1724.1988. View

17.

Saggin L, Ausoni S, Gorza L, Sartore S, Schiaffino S . Troponin T switching in the developing rat heart. J Biol Chem. 1988; 263(34):18488-92. View

18.

Saggin L, Gorza L, Ausoni S, Schiaffino S . Troponin I switching in the developing heart. J Biol Chem. 1989; 264(27):16299-302. View

19.

Lyons G, Schiaffino S, Sassoon D, Barton P, Buckingham M . Developmental regulation of myosin gene expression in mouse cardiac muscle. J Cell Biol. 1990; 111(6 Pt 1):2427-36. PMC: 2116419. DOI: 10.1083/jcb.111.6.2427. View

20.

Ng W, GRUPP I, Subramaniam A, Robbins J . Cardiac myosin heavy chain mRNA expression and myocardial function in the mouse heart. Circ Res. 1991; 68(6):1742-50. DOI: 10.1161/01.res.68.6.1742. View