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Results for “tissue specificity”

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At least 235 records · Page 13Linked to original sources

PubMed1999

Novel cis element for tissue-specific transcription of rat platelet-derived growth factor beta-receptor gene.

Platelet-derived growth factor (PDGF) and its receptors are widely expressed in several tissues in the stage of cellular growth and development. In adulthood, PDGF beta-receptor (PDGFbetaR) is mainly detected in pathological conditions such as atherosclerotic lesions and injured vascular wall. The purpose of the present study was to elucidate the underlying mechanism of PDGFbetaR gene expression under pathological conditions in vascular smooth muscle cells (VSMC) and to identify the important cis elements responsible for tissue-specific gene transcription. Gel mobility shift assay and supershift assay indicated that the CCAAT motif located at -67 (C67) was mainly interacted with NF-YC, and this element drove the basal promoter activity of the gene as a putative promoter. On the other hand, another important sequence essential for the basal transcription was found at a 30-bp region (R30) spanning -150 to -121. To test whether R30 actually regulates the tissue-specific transcription of PDGFbetaR gene, electromobility shift pattern was compared between VSMC and hepatoma cell line (HTC). We obtained the result that DNA-protein complex seen only in nuclear extracts from HTC suppressed the promoter activity in HTC in a tissue-specific manner. Furthermore, cis element decoy transfection experiments for C67 and R30 also revealed that both elements were functionally important in mRNA expression of PDGFbetaR in VSMC. From these results, we concluded that the basal activity of PDGFbetaR gene expression was transactivated by the interaction or coordination of both C67 and R30, and the latter one mainly controlled the tissue-specific gene expression in VSMC.

Animals↗

PubMed2005

Tissue-specific expression of stabilized SOLITARY-ROOT/IAA14 alters lateral root development in Arabidopsis.

Auxin is important for lateral root (LR) initiation and subsequent LR primordium development. However, the roles of tissue-specific auxin signaling in these processes are poorly understood. We analyzed transgenic Arabidopsis plants expressing the stabilized mutant INDOLE-3 ACETIC ACID 14 (IAA14)/SOLITARY-ROOT (mIAA14) protein as a repressor of the auxin response factors (ARFs), under the control of tissue-specific promoters. We showed that plants expressing the mIAA14-glucocorticoid receptor (GR) fusion protein under the control of the native IAA14 promoter had the solitary-root/iaa14 mutant phenotypes, including the lack of LR formation under dexamethasone (Dex) treatment, indicating that mIAA14-GR is functional in the presence of Dex. We then demonstrated that expression of mIAA14-GR under the control of the stele-specific SHORT-ROOT promoter suppressed LR formation, and showed that mIAA14-GR expression in the protoxylem-adjacent pericycle also blocked LR formation, indicating that the normal auxin response mediated by auxin/indole-3 acetic acid (Aux/IAA) signaling in the protoxylem pericycle is necessary for LR formation. In addition, we demonstrated that expression of mIAA14-GR under either the ARF7 or the ARF19 promoter also suppressed LR formation as in the arf7 arf19 double mutants, and that IAA14 interacted with ARF7 and ARF19 in yeasts. These results strongly suggest that mIAA14-GR directly inactivates ARF7/ARF19 functions, thereby blocking LR formation. Post-embryonic expression of mIAA14-GR under the SCARECROW promoter, which is expressed in the specific cell lineage during LR primordium formation, caused disorganized LR development. This indicates that normal auxin signaling in LR primordia, which involves the unknown ARFs and Aux/IAAs, is necessary for the establishment of LR primordium organization. Thus, our data show that tissue-specific expression of a stabilized Aux/IAA protein allows analysis of tissue-specific auxin responses in LR development by inactivating ARF functions.

Arabidopsis↗

PubMed2004

A proximal tissue-specific module and a distal negative regulatory module control apolipoprotein(a) gene transcription.

The apo(a) [apolipoprotein(a)] gene is responsible for variations in plasma lipoprotein(a), high levels of which are a risk factor for atherosclerosis and myocardial infarction. The apo(a) promoter stimulates the expression of reporter genes in HepG2 cells, but not in HeLa cells. In the present study, we demonstrate that the 1.4 kb apo(a) promoter comprises two composite regulatory regions: a distal negative regulatory module (positions -1432 to -716) and a proximal tissue-specific module (-716 to -616). The distal negative regulatory module contains two strong negative regulatory regions [polymorphic PNR (pentanucleotide repeat region) and NREbeta (negative regulatory element beta)], which sandwich the postive regulatory region PREbeta (positive regulatory element beta). The PNR was shown to bind to transcription factors in a tissue-specific manner, whereas the ubiquitous transcription factors hepatocyte nuclear factor 3alpha and GATA binding protein 4 bound to NREbeta to repress gene transcription. The proximal tissue-specific module contains two regulatory elements: an activating region (PREalpha) that activates transcription in HepG2 cells, and NREalpha, which is responsible for repressing the apo(a) gene in HeLa cells. NREalpha binds to a HeLa-specific repressor. These multiple regulatory elements might work co-operatively to finely regulate apo(a) gene expression. Although the tissue-specific module is required for apo(a) gene activation and repression in a tissue-specific manner, the combinatorial interplay of the distal and proximal regulators might define the complex pathway(s) of apo(a) gene regulation.

Apolipoproteins A↗

PubMed1990

Cooperativity of sequence elements mediates tissue specificity of the rat insulin II gene.

The 5'-flanking region of the rat insulin II gene (-448 to +50) is sufficient for tissue-specific expression. To further determine the tissue-specific cis-acting element(s), important sequences defined by linker-scanning mutagenesis were placed upstream of a heterologous promoter and transfected into insulin-producing and -nonproducing cells. Rat insulin promoter element 3 (RIPE3), which spans from -125 to -86, was shown to confer beta-cell-specific expression in either orientation. However, two subregions of RIPE3, RIPE3a and RIPE3b (defined by linker-scanning mutations), displayed only marginal activities. These results suggest that the two subregions cooperate to confer tissue specificity, presumably via their cognate binding factors.

Animals↗

PubMed1977

[Tissue specific uncoupler of mitochondrial oxidative phosphorylation].

The influence of endogenous uncoupling agent from the rat liver on oxidative phosphorylation of the liver, kidney, heart, lungs, and brain mitochondria was studied; the tissue-specificity of its action was demonstrated. The selective action of the uncoupler on the mitochondrial membrane is more obviously expressed within the range of pH 6.9--6.3 approaching such of the hepatocyte cytoplasm. The tissue-specificity was independent of the original state of mitochondria and could be eliminated only by heat injury of the oxidative phosphorylation. The activity of the tissue-specific uncoupling factor failed to diminish when the ribosomes and microsomes were removed by centrifugation. Addition of bovine albumin to the incubation medium had no influence of the value of the tissue-specific uncoupling. Participation of the uncoupler in the intratissue proliferation control is discussed.

Animals↗

PubMed1993

Tissue-specific promoters regulate aromatase cytochrome P450 expression.

In humans, estrogen biosynthesis occurs in several tissue sites, including ovary, placenta, adipose, and brain. Recent work from our laboratory indicates that tissue-specific expression of aromatase cytochrome P450 (P450arom), the enzyme responsible for estrogen biosynthesis, is determined, in part, by the use of tissue-specific promoters. Thus, the expression of P450arom in human ovary appears to utilize a promoter proximal to the translation start site. This promoter is not utilized in placenta; instead, the promoter used to drive aromatase expression in placenta is > or = 40 kb upstream from the translational start site. In addition, a minor promoter used in the expression of a small proportion of placental transcripts is 9 kb upstream from the start of translation. Transcripts from these promoters are also expressed in other fetal tissues, including placenta-related cells such as JEG-3 choriocarcinoma cells and hydatidiform moles and other fetal tissues such as fetal liver. In adipose tissue, on the other hand, expression of P450arom may be achieved by yet another, adipose-specific promoter. The various 5'-untranslated exons unique for expression driven by each of these promoters are spliced into a common intron/exon boundary upstream from the translational start site. This means that the protein expressed in each of the various tissue-specific sites of estrogen biosynthesis is identical.

Amino Acid Sequence↗

PubMed1990

Genomic structure and comparison of mouse tissue-specific alkaline phosphatase genes.

A full-length human placental alkaline phosphatase (AP) cDNA was used to identify and clone related genes from mouse genomic libraries. We report the cloning, sequence, and structural comparison of the mouse embryonic and intestinal AP genes and a putative AP pseudogene. All three mouse genes are composed of 11 exons interrupted by 10 small introns (70-261 bp) with an organization analogous to that of the three human tissue-specific AP genes. Introns interrupt the coding sequences at identical positions in all three mouse and human tissue-specific AP genes. The deduced amino acid sequence of the isozymes predicts proproteins of 529, 559, and 466 amino acids for embryonic AP, intestinal AP, and pseudo-AP, respectively. A repetitive sequence inserted in exon XI of the mouse intestinal AP gene codes for a unique stretch of 41 amino acids, 20 of which are threonines. This insertion has disrupted a region recognized as being responsible for phosphatidylinositol anchorage of human placental AP to the cytoplasmic membrane. Phylogenetic analysis indicates that the three mouse AP isozymes form a distinct group separate from the human tissue-specific AP isozymes, suggesting the taxon-specific evolution of the AP genes as opposed to independent evolution of AP genes expressed in specific tissues.

Alkaline Phosphatase↗

PubMed2001

Tissue-specific patterns of a maize Myb transcription factor are epigenetically regulated.

The maize p1 gene encodes a Myb-homologous regulator of red pigment biosynthesis. To investigate the tissue-specific regulation of the p1 gene, maize plants were transformed with constructs combining promoter and cDNA sequences of two alleles which differ in pigmentation patterns: P1-wr (white pericarp/red cob) and P1-rr (red pericarp/red cob). Surprisingly, all promoter/cDNA combinations produced transgenic plants with red pericarp and red cob (RR pattern), indicating that the P1-wr promoter and encoded protein can function in pericarp. Some of the RR patterned transgenic plants produced progeny plants with white pericarp and red cob (WR pattern), and this switch in tissue-specificity correlated with increased transgene methylation. A similar inverse correlation between pericarp pigmentation and DNA methylation was observed for certain natural p1 alleles, which have a gene structure characteristic of standard P1-wr alleles, but which confer red pericarp pigmentation and are consistently less methylated than standard P1-wr alleles. Although we cannot rule out the possible existence of tissue-specific regulatory elements within the p1 non-coding sequences or flanking regions, the data from transgenic and natural alleles suggest that the tissue-specific pigmentation pattern characteristic of the P1-wr phenotype is epigenetically controlled.

Alleles↗

PubMed1990

A factor binding GATAAG confers tissue specificity on the promoter of the human zeta-globin gene.

We describe the characterisation of cis-acting sequences which control the tissue specific expression of the human zeta globin gene. An extensive search for enhancer sequences in the vicinity of this gene proved negative. Instead our data demonstrate that the minimal promoter of the zeta gene is itself tissue specific. Sequences close to and possibly including the -100 CACCC and -70 CCAAT boxes display some erythroid specificity. However the principal tissue specific element is a GATAA sequence at -120 directly adjacent to the minimal promoter. Specific deletion of GATAA reduces zeta promoter activity 5 fold in erythroid but not non-erythroid cells. We also demonstrate that an erythroid specific factor binds to this GATAA sequence. Furthermore this factor forms a complex with the transcription factor CP1 which we show interacts with the zeta CCAAT box. We present evidence that the zeta GATAA binding factor is equivalent to GF1 recently purified and cloned by Tsai et al [1]. The erythroid specific GATAA sequence has been found in the promoters and enhancers of a number of erythroid specific genes. Similarly we show here that the zeta globin gene relies on a GATAA sequence in its promoter to specify its expression in erythroid cells.

Animals↗

PubMed1993

Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors, as well as in normal fetal and adult gonads.

We have previously demonstrated that the tissue-specific regulation of human aromatase cytochrome P450 (P450arom) gene expression is, in part, the consequence of the use of tissue-specific promoters. Promoter I.1 (PI.1) and PI.2-specific transcripts are expressed in the placenta, whereas promoter II (PII) appears to be the only active promoter in the corpus luteum. Testicular and ovarian sex cord tumors with annular tubules (SCTATs) associated with gynecomastia in prepubertal boys and isosexual precocity in girls with Peutz-Jeghers syndrome (P-JS) have been previously reported. In the present study, we investigated the regulatory elements directing P450arom gene transcription in samples of SCTAT from three prepubertal boys and a girl with P-JS and an ovarian granulosa cell tumor from an adult woman, as well as in healthy fetal and adult testicular and ovarian tissues. Placental tissue was used as a control. Using polymerase chain reaction linked to reverse transcription and northern blotting, we determined the tissue-specific use of various P450arom promoters by analyzing specific 5'-termini from messenger RNA templates. Results indicate a universal gonadal promoter (PII) directs P450arom gene expression in healthy fetal and adult ovaries and testes, as well as in SCTAT of the P-JS and an adult ovarian granulosa cell tumor. These results are interpreted to mean that use of PII in human ovary and testis is preserved from the fetal period into adult life as well as in transformed neoplastic Sertoli and granulosa cells. On the other hand, transcripts from placenta are specific for PI.1 (and to a much lesser extent, PI.2). In SCTAT, immunoreactive P450arom is detected only in the cytoplasm of neoplastic cells, whereas the normal-appearing sex cords do not contain any immunoreactive P450arom. These results further suggest that the markedly increased aromatase expression of these transformed neoplastic cells is not a consequence of using different tissue-specific promoters. Rather it appears to involve activation (or failure of inhibition) of the upstream regulatory elements of the same promoter, which is normally functional in all gonadal tissues, namely the proximal PII.

Adolescent↗

PubMed1994

Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors, as well as in normal fetal and adult gonads.

Adolescent↗

PubMed2005

Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression.

Early studies proposed that DNA methylation could have a role in regulating gene expression during development [Riggs, A.D. (1975) Cytogenet. Cell Genet. 14, 9-25]. However, some studies of DNA methylation in known tissue-specific genes during development do not support a major role for DNA methylation. In the results presented here, tissue-specific differentially methylated regions (TDMs) were first identified, and then expression of genes associated with these regions correlated with methylation status. Restriction landmark genomic scanning (RLGS) was used in conjunction with virtual RLGS to identify 150 TDMs [Matsuyama, T., Kimura, M.T., Koike, K., Abe, T., Nakao, T., Asami, T., Ebisuzaki, T., Held, W.A., Yoshida, S. & Nagase, H. (2003) Nucleic Acids Res. 31, 4490-4496]. Analysis of 14 TDMs by methylation-specific PCR and by bisulfite genomic sequencing confirms that the regions identified by RLGS are differentially methylated in a tissue-specific manner. The results indicate that 5% or more of the CpG islands are TDMs, disputing the general notion that all CpG islands are unmethylated. Some of the TDMs are within 5' promoter CpG islands of genes, which exhibit a tissue-specific expression pattern that is consistent with methylation status and a role in tissue differentiation.

Animals↗

PubMed2006

A versatile and reliable two-component system for tissue-specific gene induction in Arabidopsis.

Developmental progression and differentiation of distinct cell types depend on the regulation of gene expression in space and time. Tools that allow spatial and temporal control of gene expression are crucial for the accurate elucidation of gene function. Most systems to manipulate gene expression allow control of only one factor, space or time, and currently available systems that control both temporal and spatial expression of genes have their limitations. We have developed a versatile two-component system that overcomes these limitations, providing reliable, conditional gene activation in restricted tissues or cell types. This system allows conditional tissue-specific ectopic gene expression and provides a tool for conditional cell type- or tissue-specific complementation of mutants. The chimeric transcription factor XVE, in conjunction with Gateway recombination cloning technology, was used to generate a tractable system that can efficiently and faithfully activate target genes in a variety of cell types. Six promoters/enhancers, each with different tissue specificities (including vascular tissue, trichomes, root, and reproductive cell types), were used in activation constructs to generate different expression patterns of XVE. Conditional transactivation of reporter genes was achieved in a predictable, tissue-specific pattern of expression, following the insertion of the activator or the responder T-DNA in a wide variety of positions in the genome. Expression patterns were faithfully replicated in independent transgenic plant lines. Results demonstrate that we can also induce mutant phenotypes using conditional ectopic gene expression. One of these mutant phenotypes could not have been identified using noninducible ectopic gene expression approaches.

Arabidopsis↗

PubMed1976

Infection of developing mouse embryos with murine leukemia virus: tissue specificity and genetic transmission of the virus.

The tissue specificity of Moloney leukemia virus (M-MuLV) was studied by infecting mice at two different stages of development. Either newborn mice which can be considered as essentially fully differentiated animals were infected with M-MuLV or preimplantation mouse embryos were infected in vitro at the 4-8 cell stage, a stage of development before any differentiation has taken place. After surgical transfer to the uteri of pseudopregnant surrogate mothers, the latter developed to term and adult mice. In both cases, animals were obtained that had developed an M-MuLV induced leukemia. Molecular hybridization tests for the presence of M-MuLV-specific sequences were conducted on DNA extracted from different tissues of leukemic animals to determine which tissues were successfully infected by the virus. Mice which were infected as newborns carried M-MuLV-specific DNA sequences in "target tissues" only, i. e., thymus, spleen, lymph nodes or in organs infiltrated by tumor cells, whereas "non-target tissues" did not carry virus-specific sequences. In contrast, when leukemic animals derived from M-MuLV-infected preimplantation embryos were analyzed, virus-specific sequences were detected in target tissues as well as in non-target tissues, such as liver, kidney, brain, testes and the germ line. To study the expression of the viral DNA integrated in target and non-target organs, RNA was extracted from different tissues of an animal infected at the preimplantation stage. Fifty to 100 times more M-MuLV-specific RNA was detected in tumor tissues than was found in non-target organs. Since all organs contained the same amount of virus-specific DNA, these results indicate that the integrated virus genome can be differentially expressed in different tissues. The organ-tropism of RNA tumor viruses is discussed in view of these findings. Mice that were infected at the preimplantation stage were found to have M-MuLV integrated into their germ line. Virus transmission from the father to the offspring occurred according to simple Mendelian expectations. Molecular hybridization tests revealed that in the animals studied, the virus was integrated into the germ line at only one out of two or three possible integration sites. During the development of leukemia amplification of this virus copy was observed in the target tissues only, but not in the non-target tissues.

Animals↗

PubMed1997

Tissue-specific activation of the osmotin gene by ABA, C2H4 and NaCl involves the same promoter region.

The gene encoding the antifungal protein osmotin is induced by several hormonal and environmental signals. In this study, tissue-specific and inducer-mediated expression of the reporter gene beta-glucuronidase (uidA) fused to different fragment lengths of the osmotin promoter was evaluated in transgenic tobacco (Nicotiana tabacum). The region of the promoter between -248 to -108 (Fragment A) was found to be essential and sufficient for inducer (abscisic acid (ABA), C2H4 and NaCl)-mediated expression of the reporter gene. Expression of the reporter gene was developmentally regulated and increased with maturity of leaves, stem and flowers. Expression also was tissue-specific being most highly expressed in epidermis and vascular parenchyma of the stem. The regulators ABA, C2H4 and NaCl exhibited tissue-specific induction of this promoter. The promoter was specifically responsive to C2H4 in flowers at virtually all stages of development, but not responsive in these tissues to ABA or NaCl. Conversely, ABA and NaCl were able to induce reporter gene activity using promoter Fragment A in specific tissues of root where C2H4 was unable to induce activity. Further dissection of the promoter Fragment A into fragments containing either the conserved GCC element (PR); PR/AT; or G/AT sequences, and subsequent testing of these fragments fused to GUS in transgenic plants was performed. These experiments revealed that the promoter fragment containing PR element alone, although required, was barely able to allow responsiveness to C2H4. However, significant C2H4-induced activity was obtained with a promoter fragment containing the AT and PR elements together.

Abscisic Acid↗

PubMed1991

An upstream regulatory region mediates high-level, tissue-specific expression of the human alpha 1(I) collagen gene in transgenic mice.

Studies in vitro have not adequately resolved the role of intronic and upstream elements in regulating expression of the alpha 1(I) collagen gene. To address this issue, we generated 12 separate lines of transgenic mice with alpha 1(I) collagen-human growth hormone (hGH) constructs containing different amounts of 5'-flanking sequence, with or without most of the first intron. Transgenes driven by 2.3 kb of alpha 1(I) 5'-flanking sequence, whether or not they contained the first intron, were expressed at a high level and in a tissue-specific manner in seven out of seven independent lines of transgenic mice. In most tissues, the transgene was expressed at levels approaching that of the endogenous alpha 1(I) gene and was regulated identically with the endogenous gene as animals aged. However, in lung, expression of the transgene was anomalously high, and in muscle, expression was lower than that of the endogenous gene, suggesting that in these tissues other regions of the gene may participate in directing appropriate expression. Five lines of mice were generated containing transgenes driven by 0.44 kb of alpha 1(I) 5'-flanking sequence (with or without the first intron), and expression was detected in four out of five of these lines. The level of expression of the 0.44-kb constructs in the major collagen-producing tissues was 15- to 500-fold lower than that observed with the longer 2.3-kb promoter. While transgenes containing the 0.44-kb promoter and the first intron retained a modest degree of tissue-specific expression, those without the first intron lacked tissue specificity and were poorly expressed in all tissues except lung. These results contribute to our understanding of the role of the first intron in regulating alpha1(I) gene expression and identify a region, upstream of the basal alpha1(I) promotor, which is necessary for full tissue-specific, developmentally regulated expression of the alpha1(I) collagen gene.

Animals↗

PubMed1987

Upstream DNA sequences required for tissue-specific expression of the HLA-DR alpha gene.

We have used in vitro deletion mutagenesis in combination with DNA transfection to search for cis-acting regulatory elements involved in the tissue-specific expression of a human class II major histocompatibility complex gene. A 140-base-pair 5' flanking fragment that contains the class II box consensus sequences and an octamer sequence (ATTTGCAT) confers tissue specificity on the promoter of the HLA-DR alpha gene. Recombinant DNA plasmids containing this DR alpha gene segment fused to the coding sequence of the bacterial chloramphenicol acetyltransferase gene are expressed at higher levels in human B-cell lines than in human T-cell lines. We have demonstrated that the most 5' of the class II boxes is essential for tissue-specific DR alpha promoter function. In addition, using an electrophoretic mobility shift assay to identify DNA binding proteins, we have detected binding of nuclear proteins to DNA probes containing the class II boxes and the octamer sequence. A protein that binds to the octamer is present at higher levels in nuclear extracts of B-cell lines than in other cell lines examined. This protein may be important for the tissue-specific expression of the HLA-DR alpha gene.

B-Lymphocytes↗

PubMed1980

Evidence for a quantitative tissue-specific distribution of high mobility group chromosomal proteins.

The quantitative tissue specificity of the high mobility group (HMG) chromosomal proteins was investigated. Perchloric acid (PCA) extracts of four different chicken tissues and erythrocytes contained three proteins which comigrated on NaDodSO4-polyacrylamide gels with the HMG's 1,2, and E from erythrocyte nuclei. These three HMG's from embryonic skeletal muscle and erythrocytes also comigrated on two-dimensional gels, employing an acid-urea system in the first dimension and an NaDodSO4 system in the second. Interpretation of the two-dimensional gels suggested that the two low molecular weight proteins of this triplet arose from the HMG 2 band of the acid-urea gels. These have been designated HMG 2A and HMG 2B. Three proteins of similar molecular weights were also found in the PCA extracts of calf thymus. They were arranged in a similar but not identical pattern on two-dimensional gels. Thus, these three HMG's appear to be neither tissue nor species specific. In addition, the 2.0% PCA extracts of all chicken tissues examined contain a 38 000-dalton (38K) nuclear protein which coisolates with the HMG's. These four proteins are found in different relative amounts in each of the four chicken tissues and erythrocytes. They are found in the same relative amounts, however, in embryonic skeletal muscles from different chicken strains with widely different highly repetitive sequence content, suggesting that none of these individual proteins is selectively localized to constitutive heterochromatin. The quantitative tissue specificity of the HMG's and the 38K protein, however, suggests that they may participate in regulating cell-specific gene expression.

Animals↗