The zinc finger-only protein Zfp260 is a novel cardiac regulator and a nuclear effector of alpha1-adrenergic signaling.
alpha1-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 alpha1-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 alpha1-adrenergic stimulation. Interestingly, Zfp260 transcripts are induced by alpha1-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 alpha1-adrenergic signaling.
Debrus
Sophie
S
Unité de Recherche en Développement et Différenciation Cardiaques, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal QC H2W 1R7, Canada.
Rahbani
Loulwa
L
Marttila
Minna
M
Delorme
Bruno
B
Paradis
Pierre
P
Nemer
Mona
M
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D017930:Genes, Reporter; D006367:HeLa Cells; D006321:Heart / Q000196:embryology; D006801:Humans; D006973:Hypertension / Q000235:genetics; D006984:Hypertrophy / Q000235:genetics; D007150:Immunohistochemistry; D007763:Lac Operon; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000737:chemistry*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016335:Zinc Fingers
D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D015534:Trans-Activators; C505619:Zfp260 protein, mouse; D012313:RNA; D009320:Atrial Natriuretic Factor