Negative control elements and cAMP responsive sequences in the tissue-specific expression of mouse renin genes.

Nakamura, Norifumi; Burt, David W.; Paul, Martin; Dzau, Victor J.

doi:10.1073/pnas.86.1.56

Cited by 80 publications

(41 citation statements)

References 25 publications

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“…Single-stranded oligonucleotides were washed by 70% ethanol, dried, and dissolved in sterile Tris/EDTA buffer (10 mM Tris-HCl [pH 8.0], 1 mM EDTA). The oligonucleotides were purified over a NAP column (Pharmacia LKB, Piscataway, NJ) and quantitated by spectrophotometer.…”

Section: Methodsmentioning

confidence: 99%

“…This construct allowed an examination of the putative regulatory regions of the renin gene. Our previous biochemical and in vitro studies suggested that tissueregulated expression is dependent on a complex interaction of positive and negative transcriptional factors competing for a specific cis-region (CRE/NRE) in the 5' region of the renin gene (7,8). In the kidney the positive factor, CREB (43 kD), binds to the cis-element under basal conditions, blocking the binding of the NREB (72 kD).…”

Section: (Consensus Sequence [Tnn(t/g)tc(c/t)ca(c/g)agg])mentioning

confidence: 99%

“…This allows basal, constitutive expression of the renin gene. In extrarenal sites such as the SMG, the NREB is able to bind effectively to the region, since the CREB is inactivated by an inhibitory protein present in the extrarenal tissue, thereby inhibiting renin expression (7) (6,8). Thus, the regulation of renin expression at this sequence is similar to the dynamic interaction of nuclear factor-KB, v-rel, and inhibitor-KB or I-KB at the region of the KB sequence (30) (11).…”

Section: (Consensus Sequence [Tnn(t/g)tc(c/t)ca(c/g)agg])mentioning

confidence: 99%

“…Consequently, the NREB is able to bind to the NRE, resulting in the silencing of Renld in the SMG. On the other hand, Ren2d is expressed in the SMG because the NRE appears to be nonfunctional due to a 150-bp insertion that interrupts the NRE (8).…”

Section: Introductionmentioning

confidence: 99%

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In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer.

Yamada

Horiuchi²,

Morishita³

et al. 1995

J. Clin. Invest.

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DBA/2J mouse contains two renin gene loci (Renld and Ren2d). Ren2d but not Renl d is expressed in submandibular gland (SMG) while both are expressed in the kidney. Based on in vitro studies, we have postulated that a negative regulatory element (NRE) in the renin gene promoter is involved in its tissue-specific expression. In this study, we examined the molecular mechanism at the in vivo level using direct gene transfer. Fragments of the Renld or Ren2d promoter were fused to a chloramphenicol acetyltransferase (CAT) gene expression vector. These constructs complexed in fusogenic liposomes were injected directly into the mouse SMG or intraarterially into the mouse kidney via the renal artery. The vector containing the CAT exhibited readily detectable in vivo expressions in both SMG and kidney. In the SMG, Renld fragment containing the NRE abolished CAT expression while deletion of the NRE restored CAT expression. The homologous fragment from the Ren2d promoter did not inhibit CAT expression while deletion of the 150-bp insertion resulted in the inhibition. Cotransfection of Renld construct with Renld-NRE oligonucleotides as transcriptional factor decoy restored CAT expression. Contrary to the SMG, transfection with Renld fragment-CAT construct or Ren2d fragment-CAT construct into the kidney resulted in similar levels of CAT expression. Interestingly, human cmyc NRE oligonucleotides which share homology with Renld-NRE competed effectively with these oligonucleotides for the regulation of Renld gene expression in vivo. This NRE sequence is also homologous to silencer elements found in multiple mammalian genes, suggesting the presence of a family of NRE/NRE binding proteins regulating expression of diverse genes. (J. Clin. Invest. 1995Invest. . 96:1230Invest. -1237

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Section: Methodsmentioning

confidence: 99%

Section: (Consensus Sequence [Tnn(t/g)tc(c/t)ca(c/g)agg])mentioning

confidence: 99%

Section: (Consensus Sequence [Tnn(t/g)tc(c/t)ca(c/g)agg])mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer.

Yamada

Horiuchi²,

Morishita³

et al. 1995

J. Clin. Invest.

Self Cite

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“…3 Screening of libraries was done according to Benton and Davis. 11 DNA probes containing renin exon sequences were nick translated to a specific activity of Ϸ1.7ϫ10 6 Bq/kg and included in the hybridization mix at a concentration of 1.7ϫ10 7 Bq/L. 12 Screening of Ϸ2.5ϫ10…”

Section: Genomic Clonesmentioning

confidence: 99%

Evaluating a Model of an NRE Mediated Tissue-Specific Expression of Murine Renin Genes

et al. 2001

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Abstract-We have used comparative sequence analysis to evaluate a putative silencer element that has been proposed to be involved in the differential tissue-expression of the murine renin genes: Ren-1 and Ren-2. In the mouse, these genes share a similar pattern of tissue-specific renin expression. One significant difference is seen in the submandibular gland (SMG) where renin expression from the Ren-2 locus is 100-fold greater than the expression from the Ren-1 locus. One model proposes that this differential expression arises from the interplay among a negative regulatory element and a cAMP responsive element, their respective binding factors, and the disruption of the negative regulatory element by an insertion (M2) that is found in Ren-2 but not in Ren-1. enin is an important regulatory enzyme involved in blood pressure maintenance and electrolyte homeostasis. It catalyzes the first reaction in the production of angiotensin II, a potent vasoactive hormone that is directly involved in both the circulating and tissue-specific renin-angiotensin systems. Many inbred strains of mice, such as DBA/2, which are derived from M. domesticus and M. musculus, possess an additional copy of the renin gene. This second locus arose as a tandem duplication to Ren-1. 1,2 Precisely the same duplication event is observed in the closely related subspecies M. hortulanus and M. spretus. 3 In these mouse species, the 2 renin genes, Ren-1 and Ren-2, share overlapping but nonidentical patterns of tissue-specific expression.The primary site of synthesis for circulating renin in all mouse strains is the kidney. Multiple alleles from both Ren-1hortulanus allele) and Ren-2 (Ren-2 d ϭ Renin-2 DBA/2J allele, Ren-2 h ϭ Renin-2 M. hortulanus allele) are expressed at approximately equal levels in the kidneys from 1-or 2-gene strains of mice. 3,4 In addition, a limited spectrum of extrarenal sites of tissue-renin production, including the adrenal gland, testes, ovaries, coagulating gland, liver, and submandibular gland (SMG), has also been identified. 5 The most dramatic difference in Ren-1 and Ren-2 expression has been noted in the SMG. In 2-gene strains of mice (DBA2/J and M. hortulanus), Ren-2 expression is Ͼ100-fold higher than expression of Ren-1 transcripts. Overall, the Ren-2 d and Ren-2 h alleles show a similar expression pattern as judged by the examination of a number of tissues, including SMG, kidney, testes, coagulating gland, and liver. Ren-1 d and Ren-1 h also share a similar pattern of renin expression, differing only in the increased expression of Ren-1 h in the liver relative to Ren-1 d . 5 Dzau and his colleagues 6 -9 have proposed that the similarities seen for Ren-2 and Ren-1 expression in the kidney, versus the differences seen in the SMG of DBA/2J, result from the complex interplay among a negative regulatory element (NRE), a cAMP responsive element (CRE), and their

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Renin

Morris¹

2000

Comprehensive Physiology

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The sections in this article are: The Renin Paper A blood pressure‐raising substance is formed in the kidneys and passed into the blood Time course of the pressure elevation following injection of renin Analysis of the mechanism underlying the pressure rise Renin Release Regulation Renin Gene: Structure and Control Background Renin Gene Structure Renin Promoter Structure Renin Promoter Control Transcription Factors Renin Messenger RNA Synthesis and Activation Biosynthesis of Prorenin Processing of Prorenin Structure of Renin Binding Protein(s) of Renin Genetic Studies Studies in Rats Studies in Humans Transgenic Mice and Rats Human Gene in Mice Renin Promoter–Simian Virus 40 T Antigen Transgenic Mice Human Promoter Transgenic Mice Ren‐2 Hypertensive Transgenic Rats Model of Malignant Hypertension Renin and Angiotensinogen Transgenic Mice and Rats Knockouts Summary and Challenges

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Negative control elements and cAMP responsive sequences in the tissue-specific expression of mouse renin genes.

Cited by 80 publications

References 25 publications

In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer.

In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer.

Evaluating a Model of an NRE Mediated Tissue-Specific Expression of Murine Renin Genes

Renin

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