scholarly journals Jumonji Represses Atrial Natriuretic Factor Gene Expression by Inhibiting Transcriptional Activities of Cardiac Transcription Factors

2004 ◽  
Vol 24 (23) ◽  
pp. 10151-10160 ◽  
Author(s):  
Tae-gyun Kim ◽  
Junqin Chen ◽  
Junich Sadoshima ◽  
Youngsook Lee
Keyword(s):  
Gene Expression ◽  
Protein Interaction ◽  
Binding Sites ◽  
Heart Development ◽  
Atrial Natriuretic Factor ◽  
Consensus Sequence ◽  
Cardiac Differentiation ◽  
Protein Protein Interaction ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

ABSTRACT Mice with a homozygous knockout of the jumonji (jmj) gene showed abnormal heart development and defective regulation of cardiac-specific genes, including the atrial natriuretic factor (ANF). ANF is one of the earliest markers of cardiac differentiation and a hallmark for cardiac hypertrophy. Here, we show that JMJ represses ANF gene expression by inhibiting transcriptional activities of Nkx2.5 and GATA4. JMJ represses the Nkx2.5- or GATA4-dependent activation of the reporter genes containing the ANF promoter-enhancer or containing the Nkx2.5 or GATA4-binding consensus sequence. JMJ physically associates with Nkx2.5 and GATA4 in vitro and in vivo as determined by glutathione S-transferase pull-down and immunoprecipitation assays. Using mutational analyses, we mapped the protein-protein interaction domains in JMJ, Nkx2.5, and GATA4. We identified two DNA-binding sites of JMJ in the ANF enhancer by gel mobility shift assays. However, these JMJ-binding sites do not seem to mediate ANF repression by JMJ. Mutational analysis of JMJ indicates that the protein-protein interaction domain of JMJ mediates the repression of ANF gene expression. Therefore, JMJ may play important roles in the down-regulation of ANF gene expression and in heart development.

scholarly journals The Cardiac Tissue-Restricted Homeobox Protein Csx/Nkx2.5 Physically Associates with the Zinc Finger Protein GATA4 and Cooperatively Activates Atrial Natriuretic Factor Gene Expression

1998 ◽  
Vol 18 (6) ◽  
pp. 3120-3129 ◽  
Author(s):  
Youngsook Lee ◽  
Tetsuo Shioi ◽  
Hideko Kasahara ◽  
Shawn M. Jobe ◽  
Russell J. Wiese ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zinc Finger ◽  
Protein Interaction ◽  
Binding Sites ◽  
Atrial Natriuretic Factor ◽  
Target Gene ◽  
Cardiac Tissue ◽  
Zinc Finger Protein ◽  
Finger Protein ◽  
Homeobox Protein

ABSTRACT Specification and differentiation of the cardiac muscle lineage appear to require a combinatorial network of many factors. The cardiac muscle-restricted homeobox protein Csx/Nkx2.5 (Csx) is expressed in the precardiac mesoderm as well as the embryonic and adult heart. Targeted disruption of Csx causes embryonic lethality due to abnormal heart morphogenesis. The zinc finger transcription factor GATA4 is also expressed in the heart and has been shown to be essential for heart tube formation. GATA4 is known to activate many cardiac tissue-restricted genes. In this study, we tested whether Csx and GATA4 physically associate and cooperatively activate transcription of a target gene. Coimmunoprecipitation experiments demonstrate that Csx and GATA4 associate intracellularly. Interestingly, in vitro protein-protein interaction studies indicate that helix III of the homeodomain of Csx is required to interact with GATA4 and that the carboxy-terminal zinc finger of GATA4 is necessary to associate with Csx. Both regions are known to directly contact the cognate DNA sequences. The promoter-enhancer region of the atrial natriuretic factor (ANF) contains several putative Csx binding sites and consensus GATA4 binding sites. Transient-transfection assays indicate that Csx can activate ANF reporter gene expression to the same extent that GATA4 does in a DNA binding site-dependent manner. Coexpression of Csx and GATA4 synergistically activates ANF reporter gene expression. Mutational analyses suggest that this synergy requires both factors to fully retain their transcriptional activities, including the cofactor binding activity. These results demonstrate the first example of homeoprotein and zinc finger protein interaction in vertebrates to cooperatively regulate target gene expression. Such synergistic interaction among tissue-restricted transcription factors may be an important mechanism to reinforce tissue-specific developmental pathways.

Atrial natriuretic factor binding sites in the jejunum

1989 ◽  
Vol 256 (2) ◽  
pp. G436-G441 ◽  
Author(s):  
C. Bianchi ◽  
G. Thibault ◽  
A. De Lean ◽  
J. Genest ◽  
M. Cantin
Keyword(s):  
Binding Sites ◽  
Atrial Natriuretic Factor ◽  
Specific Binding ◽  
Rat Tissues ◽  
Rat Jejunum ◽  
Specific Binding Sites ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

We have studied the localization and the characterization of atrial natriuretic factor (ANF) binding sites by radioautographic techniques. Quantitative in vitro radioautography with a computerized microdensitometer demonstrated the presence of high-affinity, low-capacity 125I-ANF-(99-126) binding sites (Kd, 48 pM; Bmax, 63 fmol/mg protein) mainly in the villi of 20-microns slide-mounted transverse sections of the rat jejunum. Competition curves showed 50% inhibitory concentrations of 55 and 1,560 pM for ANF-(99-126) and ANF-(103-123), respectively. In vivo electron microscope radioautography showed that 80% of the silver grains were localized on the lamina propria fibroblast-like cells, 18% on mature enterocytes, and 2% on capillaries. Bradykinin and adrenocorticotropin did not compete with ANF binding. These results demonstrate that ANF binding sites in the rat jejunum possess the pharmacological characteristics of functional ANF receptors encountered in other rat tissues, and ultrastructural radioautographs show their cellular distribution. Taken together, these results demonstrate the presence and the localization of specific binding sites for ANF in the jejunal villi of the rat small intestine.

Distinct localization of atrial natriuretic factor and angiotensin II binding sites in the glomerulus

1986 ◽  
Vol 251 (4) ◽  
pp. F594-F602 ◽  
Author(s):  
C. Bianchi ◽  
J. Gutkowska ◽  
G. Thibault ◽  
R. Garcia ◽  
J. Genest ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Comparative Study ◽  
Binding Sites ◽  
Atrial Natriuretic Factor ◽  
Mesangial Cells ◽  
Ang Ii ◽  
Half Maximum ◽  
Natriuretic Factor ◽  
Glomerular Size ◽  
Atrial Natriuretic

A comparative study of the localization of 125I-labeled atrial natriuretic factor (ANF) and 125I-labeled angiotensin II (ANG II) binding sites in the glomerulus of the rat, after an intravascular injection, has been done by ultrastructural radioautography. 125I-ANF binding sites are localized predominantly on the podocytes of the visceral epithelium (63%) followed by the endothelium of capillaries (14%), the parietal epithelium (13%), and finally mesangial cells (10%). In a comparative study, it was confirmed that 125I-ANG II uptake is localized predominantly on mesangial cells (60%) followed by epithelial visceral cells (23%) and the endothelium of capillaries (16%). Using isolated rat glomeruli, it was confirmed that ANG II decreases glomerular size (maximum effect of 15%) with an apparent half maximum effective concentration (EC50) between 10(-9) and 10(-8) M. Although ANF alone has no apparent effect on glomerular size, it inhibits the contractile effect of ANG II with a half maximum inhibitory concentration (IC50) between 10(-11) and 10(-10) M. These results suggest that an intraglomerular mechanism other than glomerular arteriolar resistance may be involved in the modulation of glomerular filtration rate by ANF. The presence of 125I-ANF uptake mainly in foot processes of visceral epithelial cells of glomeruli in vivo and the inhibition of ANG II decrease in glomerular size by ANF in vitro raise the possibility that ANF may regulate the ultrafiltration coefficient by two mechanisms: modulation of glomerular permeability, and surface area.

scholarly journals Localization of 125I-atrial natriuretic factor (ANF)-binding sites in rat renal medulla. A light and electron microscope autoradiographic study.

1987 ◽  
Vol 35 (2) ◽  
pp. 149-153 ◽  
Author(s):  
C Bianchi ◽  
J Gutkowska ◽  
R Garcia ◽  
G Thibault ◽  
J Genest ◽  
...  
Keyword(s):  
Electron Microscope ◽  
Binding Sites ◽  
Atrial Natriuretic Factor ◽  
Renal Medulla ◽  
Microscopic Level ◽  
Electron Microscopic Level ◽  
Natriuretic Factor ◽  
Vasa Recta ◽  
Collecting Ducts ◽  
Atrial Natriuretic

Using light and electron microscope autoradiography in vivo, the localization of 125I-(Arg 101-Tyr 126) atrial natriuretic factor (ANF)-binding sites was studied in the renal medulla of rats. At the light microscopic level, the autoradiographic reaction was mainly distributed in patches in the outer medulla, and followed the tubular architecture in the innermost part of the inner medulla. At the electron microscopic level, binding sites were mainly found in the outer medullary descending vasa recta and inner medullary collecting ducts. These results suggest that, in rats, the renal medulla may participate in the natriuresis and diuresis produced by ANF through vascular and tubular effects; the former by changing medullary blood flow at the level of descending vasa recta and the latter by acting on electrolyte and water transport at the level of collecting ducts.

Atrial natriuretic factor (ANF) binding sites in brain and related structures

Peptides ◽  
1984 ◽  
Vol 5 (6) ◽  
pp. 1167-1172 ◽  
Author(s):  
Rémi Quirion ◽  
Michel Dalpé ◽  
André De Lean ◽  
J. Gutkowska ◽  
Marc Cantin ◽  
...  
Keyword(s):  
Binding Sites ◽  
Atrial Natriuretic Factor ◽  
Natriuretic Factor ◽  
Atrial Natriuretic
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