Presence of transcription regulatory elements within an intron of the virus-inducible murine TIMP gene

1988 ◽  
Vol 8 (8) ◽  
pp. 3227-3234
Author(s):  
B Coulombe ◽  
A Ponton ◽  
L Daigneault ◽  
B R Williams ◽  
D Skup
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Phorbol Esters ◽  
Marker Gene ◽  
Constitutive Expression ◽  
Regulatory Elements ◽  
Functional Assay ◽  
Rnase Protection ◽  
Intron 1 ◽  
Timp Gene

The expression of the gene for the murine tissue inhibitor of metalloproteinases (TIMP) is induced in response to viruses, growth factors, and phorbol esters. In this report we show that the accumulation of TIMP mRNA after Newcastle disease virus induction is caused by transcriptional activation of the gene. Comparison of the sequences of cDNA and genomic clones along with RNase protection and primer extension analyses revealed that the murine TIMP gene possesses multiple cap sites and that the exon 1 consists exclusively of 5'-noncoding sequences. We observed that DNA regions analogous to those found upstream of the virus-inducible interferon genes are present within intron 1 of the TIMP gene. To investigate the possible role of TIMP intron 1 in gene expression, we used a functional assay based on the transfection of plasmids in which the DNA segment to be tested is placed in proximity to a marker gene driven by the heterologous herpes simplex virus thymidine kinase promoter. Our results indicate that TIMP intron 1 contains DNA sequence elements capable of modulating the activity of a heterologous promoter in two different ways: (i) by enhancing constitutive expression and (ii) by conferring virus inducibility. These results suggest that intron 1 may be involved in the transcriptional regulation of TIMP gene expression.

scholarly journals Presence of transcription regulatory elements within an intron of the virus-inducible murine TIMP gene.

1988 ◽  
Vol 8 (8) ◽  
pp. 3227-3234 ◽  
Author(s):  
B Coulombe ◽  
A Ponton ◽  
L Daigneault ◽  
B R Williams ◽  
D Skup
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Phorbol Esters ◽  
Marker Gene ◽  
Constitutive Expression ◽  
Regulatory Elements ◽  
Functional Assay ◽  
Rnase Protection ◽  
Intron 1 ◽  
Timp Gene

The expression of the gene for the murine tissue inhibitor of metalloproteinases (TIMP) is induced in response to viruses, growth factors, and phorbol esters. In this report we show that the accumulation of TIMP mRNA after Newcastle disease virus induction is caused by transcriptional activation of the gene. Comparison of the sequences of cDNA and genomic clones along with RNase protection and primer extension analyses revealed that the murine TIMP gene possesses multiple cap sites and that the exon 1 consists exclusively of 5'-noncoding sequences. We observed that DNA regions analogous to those found upstream of the virus-inducible interferon genes are present within intron 1 of the TIMP gene. To investigate the possible role of TIMP intron 1 in gene expression, we used a functional assay based on the transfection of plasmids in which the DNA segment to be tested is placed in proximity to a marker gene driven by the heterologous herpes simplex virus thymidine kinase promoter. Our results indicate that TIMP intron 1 contains DNA sequence elements capable of modulating the activity of a heterologous promoter in two different ways: (i) by enhancing constitutive expression and (ii) by conferring virus inducibility. These results suggest that intron 1 may be involved in the transcriptional regulation of TIMP gene expression.

scholarly journals Transcriptional activation and repression by Fos are independent functions: the C terminus represses immediate-early gene expression via CArG elements.

1990 ◽  
Vol 10 (8) ◽  
pp. 4243-4255 ◽  
Author(s):  
D Gius ◽  
X M Cao ◽  
F J Rauscher ◽  
D R Cohen ◽  
T Curran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Early Gene ◽  
Immediate Early ◽  
Striking Similarity ◽  
Independent Functions

The Fos-Jun complex has been shown to activate transcription through the regulatory element known as the AP-1 binding site. We show that Fos down regulates several immediate-early genes (c-fos, Egr-1, and Egr-2) after mitogenic stimulation. Specifically, we demonstrate that the target for this repression is a sequence of the form CC(A/T)6GG, also known as a CArG box. Whereas Fos bound to the AP-1 site through a domain rich in basic amino acids and associated with Jun via a leucine zipper interaction, mutant Fos proteins lacking these structures were still capable of causing repression. Furthermore, Jun neither enhanced nor inhibited down regulation by Fos. Critical residues required for repression are located within the C-terminal 27 amino acids of c-Fos, since v-Fos and C-terminal truncations of c-Fos did not down regulate. In addition, transfer of 180 c-Fos C-terminal amino acids to Jun conferred upon it the ability to repress. Finally, Fra-1, a Fos-related protein which has striking similarity to Fos in its C-terminal 40 amino acids, also down regulated Egr-1 expression. Thus, Fos is a transcriptional regulator that can activate or repress gene expression by way of two separate functional domains that act on distinct regulatory elements.

scholarly journals Downregulation of c-fms gene expression in human monocytes treated with phorbol esters and colony-stimulating factor 1

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 123-129 ◽  
Author(s):  
E Sariban ◽  
K Imamura ◽  
M Sherman ◽  
V Rothwell ◽  
P Pantazis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Esters ◽  
Constitutive Expression ◽  
Human Monocytes ◽  
Colony Stimulating Factor ◽  
Protein Levels ◽  
Kinase C ◽  
Stimulating Factor

Abstract The colony-stimulating factor-1 (CSF-1) regulates survival, growth, and differentiation of monocytes by binding to a single class of high- affinity receptors. The CSF-1 receptor is identical to the product of the c-fms protooncogene. The present studies monitored the effects of TPA and CSF-1 on c-fms gene expression in human monocytes. The results demonstrate that TPA downmodulates the constitutive expression of c-fms mRNA to low but detectable levels. Treatment of human monocytes with TPA was similarly associated with decreases in levels of the 138- and 125-Kd c-fms-encoded proteins. However, the kinetics of c-fms protein downmodulation indicated independent effects of TPA on c-fms expression at the RNA and protein levels. Furthermore, c-fms protein levels subsequently recovered despite persistently low levels of c-fms mRNA. Although previous studies demonstrated that c-fms protein is down- regulated in the presence of CSF-1, the present results indicate that CSF-1 also downregulates levels of c-fms mRNA. Moreover, the results indicate that CSF-1 increases protein kinase C activity in the membrane fraction. Together, these findings suggest that c-fms gene expression is differentially regulated at both the RNA and protein levels after activation of protein kinase C in human monocytes treated with TPA and CSF-1.

scholarly journals Targeted inactivation of the major positive regulatory element (HS-40) of the human alpha-globin gene locus

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1202-1211 ◽  
Author(s):  
A Bernet ◽  
S Sabatier ◽  
DJ Picketts ◽  
R Ouazana ◽  
F Morle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Locus ◽  
Regulatory Element ◽  
Globin Gene ◽  
Marker Gene ◽  
Regulatory Elements ◽  
Target System ◽  
Flp Recombinase ◽  
Alpha Globin ◽  
Globin Gene Expression

Abstract We have examined the role of the major positive upstream regulatory element of the human alpha-globin gene locus (HS-40) in its natural chromosomal context. Using homologous recombination, HS-40 was replaced by a neo marker gene in a mouse erythroleukemia hybrid cell line containing a single copy of human chromosome 16. In clones from which HS-40 had been deleted, human alpha-globin gene expression was severely reduced, although basal levels of alpha 1 and alpha 2-globin mRNA expression representing less than 3% of the level in control cell lines were detected. Deletion of the neo marker gene, by using FLP recombinase/FLP recombinase target system, proved that the phenotype observed was not caused by the regulatory elements of this marker gene. In the targeted clones, deletion of HS-40 apparently does not affect long-range or local chromatin structure at the alpha promoters. Therefore, these results indicate that, in the experimental system used, HS-40 behaves as a strong inducible enhancer of human alpha- globin gene expression.

scholarly journals Mutations in the Regulatory Gene hrpG ofXanthomonas campestris pv. vesicatoria Result in Constitutive Expression of All hrp Genes

1999 ◽  
Vol 181 (21) ◽  
pp. 6828-6831 ◽  
Author(s):  
Kai Wengelnik ◽  
Ombeline Rossier ◽  
Ulla Bonas
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Transcriptional Activation ◽  
Xanthomonas Campestris ◽  
Regulatory Gene ◽  
Constitutive Expression ◽  
Amino Acid Substitutions ◽  
Pathogenicity Genes ◽  
Hrp Genes ◽  
Related Proteins

ABSTRACT hrpG is a key regulatory gene for transcriptional activation of pathogenicity genes (hrp) ofXanthomonas campestris pv. vesicatoria. We identified three mutations in hrpG which render hrp gene expression constitutive in normally suppressing medium. The mutations in hrpG result in novel amino acid substitutions compared to mutations in related proteins, such as OmpR. In addition, mutatedhrpG enhances the timing and intensity of plant reactions in infection assays.

scholarly journals Overexpression of Pti5 in Tomato Potentiates Pathogen-Induced Defense Gene Expression and Enhances Disease Resistance to Pseudomonas syringae pv. tomato

2001 ◽  
Vol 14 (12) ◽  
pp. 1453-1457 ◽  
Author(s):  
Ping He ◽  
Randall F. Warren ◽  
Tiehan Zhao ◽  
Libo Shan ◽  
Lihuang Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Disease Resistance ◽  
Pseudomonas Syringae ◽  
Transcriptional Activation ◽  
Induced Defense ◽  
Constitutive Expression ◽  
Disease Resistance Gene ◽  
Defense Gene Expression ◽  
Positive Role ◽  
Defense Gene

The tomato Pti5 gene encodes a pathogen-inducible ethylene response element-binding protein-like transcription factor that interacts with the disease resistance gene product Pto. Overexpression of Pti5 or Pti5-VP16, a translational fusion with a constitutive transcriptional activation domain, in tomato enhanced resistance to Pseudomonas syringae pv. tomato. Constitutive expression of Pti5 or Pti5-VP16 did not affect the basal level of pathogenesis-related gene expression, but it accelerated pathogen-induced expression of GluB and Catalase. The results demonstrate a positive role of Pti5 in defense gene regulation and disease resistance and suggest that a pathogen-activated posttran-scriptional regulatory step is necessary for the pathogen induction of the defense gene expression.

scholarly journals Transcriptional Activation Signals Found in the Epstein-Barr Virus (EBV) Latency C Promoter Are Conserved in the Latency C Promoter Sequences from Baboon and Rhesus Monkey EBV-Like Lymphocryptoviruses (Cercopithicine Herpesviruses 12 and 15)

1999 ◽  
Vol 73 (1) ◽  
pp. 826-833 ◽  
Author(s):  
Ezequiel M. Fuentes-Pananá ◽  
Sankar Swaminathan ◽  
Paul D. Ling
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Transcription Initiation ◽  
Epstein Barr Virus ◽  
Rhesus Macaques ◽  
Regulatory Elements ◽  
Mobility Shift ◽  
Barr Virus ◽  
Epstein Barr ◽  
Transformed Cell Lines

ABSTRACT The Epstein-Barr virus (EBV) EBNA2 protein is a transcriptional activator that controls viral latent gene expression and is essential for EBV-driven B-cell immortalization. EBNA2 is expressed from the viral C promoter (Cp) and regulates its own expression by activating Cp through interaction with the cellular DNA binding protein CBF1. Through regulation of Cp and EBNA2 expression, EBV controls the pattern of latent protein expression and the type of latency established. To gain further insight into the important regulatory elements that modulate Cp usage, we isolated and sequenced the Cp regions corresponding to nucleotides 10251 to 11479 of the EBV genome (−1079 to +144 relative to the transcription initiation site) from the EBV-like lymphocryptoviruses found in baboons (herpesvirus papio; HVP) and Rhesus macaques (RhEBV). Sequence comparison of the approximately 1,230-bp Cp regions from these primate viruses revealed that EBV and HVP Cp sequences are 64% conserved, EBV and RhEBV Cp sequences are 66% conserved, and HVP and RhEBV Cp sequences are 65% conserved relative to each other. Approximately 50% of the residues are conserved among all three sequences, yet all three viruses have retained response elements for glucocorticoids, two positionally conserved CCAAT boxes, and positionally conserved TATA boxes. The putative EBNA2 100-bp enhancers within these promoters contain 54 conserved residues, and the binding sites for CBF1 and CBF2 are well conserved. Cp usage in the HVP- and RhEBV-transformed cell lines was detected by S1 nuclease protection analysis. Transient-transfection analysis showed that promoters of both HVP and RhEBV are responsive to EBNA2 and that they bind CBF1 and CBF2 in gel mobility shift assays. These results suggest that similar mechanisms for regulation of latent gene expression are conserved among the EBV-related lymphocryptoviruses found in nonhuman primates.

scholarly journals Downregulation of c-fms gene expression in human monocytes treated with phorbol esters and colony-stimulating factor 1

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 123-129 ◽  
Author(s):  
E Sariban ◽  
K Imamura ◽  
M Sherman ◽  
V Rothwell ◽  
P Pantazis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Esters ◽  
Constitutive Expression ◽  
Human Monocytes ◽  
Colony Stimulating Factor ◽  
Protein Levels ◽  
Kinase C ◽  
Stimulating Factor

The colony-stimulating factor-1 (CSF-1) regulates survival, growth, and differentiation of monocytes by binding to a single class of high- affinity receptors. The CSF-1 receptor is identical to the product of the c-fms protooncogene. The present studies monitored the effects of TPA and CSF-1 on c-fms gene expression in human monocytes. The results demonstrate that TPA downmodulates the constitutive expression of c-fms mRNA to low but detectable levels. Treatment of human monocytes with TPA was similarly associated with decreases in levels of the 138- and 125-Kd c-fms-encoded proteins. However, the kinetics of c-fms protein downmodulation indicated independent effects of TPA on c-fms expression at the RNA and protein levels. Furthermore, c-fms protein levels subsequently recovered despite persistently low levels of c-fms mRNA. Although previous studies demonstrated that c-fms protein is down- regulated in the presence of CSF-1, the present results indicate that CSF-1 also downregulates levels of c-fms mRNA. Moreover, the results indicate that CSF-1 increases protein kinase C activity in the membrane fraction. Together, these findings suggest that c-fms gene expression is differentially regulated at both the RNA and protein levels after activation of protein kinase C in human monocytes treated with TPA and CSF-1.

scholarly journals Endogenous Retroviruses Function as Gene Expression Regulatory Elements During Mammalian Pre-implantation Embryo Development

2019 ◽  
Vol 20 (3) ◽  
pp. 790 ◽  
Author(s):  
Bo Fu ◽  
Hong Ma ◽  
Di Liu
Keyword(s):  
Gene Expression ◽  
Embryo Development ◽  
Transcriptional Activation ◽  
Nuclear Transfer ◽  
Regulatory Elements ◽  
Endogenous Retroviruses ◽  
Maternal Control ◽  
Close Relationship ◽  
Genome Activation ◽  
Zygotic Genome

Pre-implantation embryo development encompasses several key developmental events, especially the activation of zygotic genome activation (ZGA)-related genes. Endogenous retroviruses (ERVs), which are regarded as “deleterious genomic parasites”, were previously considered to be “junk DNA”. However, it is now known that ERVs, with limited conservatism across species, mediate conserved developmental processes (e.g., ZGA). Transcriptional activation of ERVs occurs during the transition from maternal control to zygotic genome control, signifying ZGA. ERVs are versatile participants in rewiring gene expression networks during epigenetic reprogramming. Particularly, a subtle balance exists between ERV activation and ERV repression in host–virus interplay, which leads to stage-specific ERV expression during pre-implantation embryo development. A large portion of somatic cell nuclear transfer (SCNT) embryos display developmental arrest and ZGA failure during pre-implantation embryo development. Furthermore, because of the close relationship between ERV activation and ZGA, exploring the regulatory mechanism underlying ERV activation may also shed more light on the enigma of SCNT embryo development in model animals.

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