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Molecular and Cellular Biology, October 2005, p. 8669-8682, Vol. 25, No. 19
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.19.8669-8682.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Zinc Finger-Only Protein Zfp260 Is a Novel Cardiac Regulator and a Nuclear Effector of {alpha}1-Adrenergic Signaling

Sophie Debrus,1 Loulwa Rahbani,1,2 Minna Marttila,1 Bruno Delorme,1 Pierre Paradis,1 and Mona Nemer1,2*

Unité de Recherche en Développement et Différenciation Cardiaques, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada,1 Département de Pharmacologie, Université de Montréal, Montréal, Québec H3C 3J7, Canada2

Received 5 May 2005/ Returned for modification 4 June 2005/ Accepted 2 July 2005

{alpha}1-Adrenergic receptors mediate several biological effects of catecholamines, including the regulation of myocyte growth and contractility and transcriptional regulation of the atrial natriuretic factor (ANF) gene whose promoter contains an {alpha}1-adrenergic response element. The nuclear pathways and effectors that link receptor activation to genetic changes remain poorly understood. Here, we describe the isolation by the yeast one-hybrid system of a cardiac cDNA encoding a novel nuclear zinc finger protein, Zfp260, belonging to the Krüppel family of transcriptional regulators. Zfp260 is highly expressed in the embryonic heart but is downregulated during postnatal development. Functional studies indicate that Zfp260 is a transcriptional activator of ANF and a cofactor for GATA-4, a key cardiac regulator. Knockdown of Zfp260 in cardiac cells decreases endogenous ANF gene expression and abrogates its response to {alpha}1-adrenergic stimulation. Interestingly, Zfp260 transcripts are induced by {alpha}1-adrenergic agonists and are elevated in genetic models of hypertension and cardiac hypertrophy. The data identify Zfp260 as a novel transcriptional regulator in normal and pathological heart development and a nuclear effector of {alpha}1-adrenergic signaling.

* Corresponding author. Mailing address: Unité de Recherche en Développement et Différenciation Cardiaques, Institut de Recherches Cliniques de Montréal, 110, Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada. Phone: (514) 987-5680. Fax: (514) 987-5575. E-mail: mona.nemer{at}ircm.qc.ca.

Molecular and Cellular Biology, October 2005, p. 8669-8682, Vol. 25, No. 19
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.19.8669-8682.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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