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At least 163 records · Page 9Linked to original sources

Complex cis-acting regulators and locus structure of Drosophila tissue-specific ADH variants.

Diverse patterns of tissue-specific expression of alcohol dehydrogenase (ADH) among species of the grimshawi subgroup of Hawaiian picture-winged Drosophila suggests control by complex or multiple, independently acting regulatory elements. These elements act by controlling Adh mRNA accumulation in individual tissue types. Restriction mapping of the Adh loci from these species reveals several insertion/deletion differences, one of which lies just outside the 5' end of the structural sequences and correlates with differences in larval patterns of ADH expression. No tissue-specific rearrangement of Adh sequences was observed.

Alcohol Dehydrogenase↗

The binding site of a steroid hormone receptor-like protein within the Drosophila Adh adult enhancer is required for high levels of tissue-specific alcohol dehydrogenase expression.

Developmental and tissue-specific transcription from the Adh distal promoter is regulated in part by the Adh adult enhancer, located 450 to 600 bp upstream from the distal RNA start site. We have characterized four proteins (DEP1 to DEP4), present in Drosophila tissue culture cell nuclear extracts, which bind to this enhancer. DEP1 and DEP2 bind to a positive cis-acting element (-492 to -481) and share nucleotide contacts. A small linker replacement deletion mutation, which disrupts the overlapping DEP1- and DEP2-binding sites, reduces Adh distal transcription in an alcohol dehydrogenase (ADH)-expressing cultured cell line, in the adult fat body (the major tissue of ADH expression), as well as in some but not all adult tissues where ADH is normally expressed. This enhancer element contains an imperfect palindromic sequence similar to steroid hormone receptor superfamily response elements. Binding-site screening of a lambda gt11 expression library has identified the steroid receptor superfamily member fushi tarazu factor 1 (FTZ-F1) as a protein that binds to this site. Anti-FTZ-F1 antibodies have identified DEP1 as FTZ-F1. DEP2 also binds to the FTZ-F1 site from the fushi tarazu zebra element, suggesting that DEP2 may also be a steroid receptor superfamily member. Our results raise the possibility that Adh regulation in certain adult tissues involves a hormone-mediated pathway. Because DEP1 (FTZ-F1) and DEP2 contact some of the same nucleotides within the positive cis element, it is unlikely that they can bind simultaneously. Such alternative binding may play a role in the tissue-specific and developmental transcription of Adh.

Alcohol Dehydrogenase↗

[Ultrastructural tissue-specific signs of the cells of cancerous tumors of the human breast].

Ultrastructural analysis of mammary carcinoma (45 cases) and its metastasis in the lymph nodes (21 cases) revealed the tissue specific features of the mammary gland: big ducts and intercellular canaliculi, microvilli, various specialized cell-to-cell contacts, basal membrane. Tissue specific features are not associated with a certain organ. In mammary carcinoma, they are more pronounced in carcinomas in situ, invasive tumours of the 1st grade of malignancy (adenocarcinoma) and specific histologic variants. They are less pronounced in solid and scirrhous invasive tumours of the 2nd and especially 3rd grade of malignancy. However it is impossible to conclude about the anaplasia degree on the basis of the number of and the correlation between various tissue specific features. Metastasis retains the capacity of cancer cells to form the tissue specific ultrastructural elements. The tissue specific properties of mammary carcinoma determine the diagnosis in cases when the question on the tissue origin of the tumour is to be solved.

Basement Membrane↗

Analysis of tissue-specific methylation patterns of mouse mammary tumor virus DNA by two-dimensional Southern blotting.

We used a two-dimensional Southern blotting procedure to analyze the tissue-specific methylation patterns of the five endogenous mouse mammary tumor viruses in the GR/A mouse strain. Our findings suggest that in certain tissues (brain, kidney, and liver) all proviruses are extensively methylated. In other tissues (spleen, placenta, and testes) all proviruses are hypomethylated to some degree. In these tissues individual proviruses display both quantitative and qualitative differences in methylation. We interpret the general patterns of tissue-specific hypomethylation in terms of a "hitch-hiker" model: mouse mammary tumor virus proviral methylation patterns reflect the tissue-specific activity of neighboring sequences. The observation that certain sites on particular proviruses are differentially methylated in a tissue-specific fashion may reflect tissue-specific differences in the makeup or conformation, or both, of proviral-containing chromatin.

Animals↗

TISA: tissue-specific alternative splicing in human and mouse genes.

Alternative splicing (AS) is a mechanism by which multiple transcripts are produced from a single gene and is thought to be an important mechanism for tissue-specific expression of transcript isoforms. Here, we report a novel graphing method for transcript reconstruction and statistical prediction of tissue-specific AS. We applied three selection steps to generate the splice graph and predict the transcript isoforms: (i) a custom scoring rule for exon/intron sets, (ii) binomial statistics for selecting valid alternative splicing with a frequency of at least 1% for the predominant form and (iii) evaluation of transcript structure. We obtained 97 286 and 66 022 valid transcripts from 26 143 human and 27 741 mouse genes, respectively. In addition, we discovered 33 481 AS events for nine types of AS patterns in human. The statistical significance of tissue specificity for each gene, transcript and AS event was assessed based on EST tissue information, followed by a multiple testing correction procedure. In human, 12 711 genes, 16 016 transcripts and 1035 AS events were predicted to be tissue-specific (false discovery rate <0.01). This information on genes, transcript structures, AS events and their tissue specificities in human and mouse are freely accessible on the TISA website (http://tisa.kribb.re.kr/AGC/).

Alternative Splicing↗

Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle.

Hormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (-40%) and TG (-63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (-90%) and strongly decreased ketone body concentrations in plasma (-80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an "anti-atherogenic" lipoprotein profile.

Adipose Tissue↗

Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue.

Estrogen biosynthesis is catalyzed by a microsomal enzyme, aromatase cytochrome P450 (P450arom; the product of the CYP19 gene). The human CYP19 gene comprises nine coding exons, II-X. Additionally, tissue-specific expression is determined by the use of tissue-specific promoters, which give rise to P450arom transcripts with unique 5'-noncoding sequences. In placenta, P450arom transcripts contain one of two 5'-untranslated exons, I.1 or I.2, while ovarian transcripts instead contain sequence consistent with the use of a promoter, PII, which is proximal to the start of translation. To characterize transcripts present in adipose tissue and adipose stromal cells (ASC) in culture, cDNA libraries were constructed by the RACE (rapid amplification of cDNA ends) procedure. Four P450arom transcripts with unique 5' termini were identified, leading to the characterization of two unique 5'-untranslated exons of the CYP19 gene, I.3 and I.4. Whereas I.3-specific sequence is expressed in adipose tissue as well as in ACS maintained under all culture conditions, I.4-specific sequence is apparently present only in breast adipose tissue, and ACS stimulated with glucocorticoids. On the other hand, PII-specific sequence is present only in cells stimulated with cAMP analogues and is absent from cells stimulated with glucocorticoids. We conclude that CYP19 gene expression in human adipose tissue likely utilizes two novel promoters and, furthermore, that alternative promoter usage in cultured ASC is a function of the hormonal environment in which the cells are maintained.

Adipose Tissue↗

No evidence for tissue-specific adaptation of synonymous codon usage in humans.

It has been proposed that the synonymous codon usage of human tissue-specific genes was under selective pressure to modulate the expression of proteins by codon-mediated translational control (Plotkin, J. B., H. Robins, and A. J. Levine. 2004. Tissue-specific codon usage and the expression of human genes. Proc. Natl. Acad. Sci. USA 101:12588-12591.) To test this model, we analyzed by internal correspondence analysis the codon usage of 2,126 human tissue-specific genes expressed in 18 different tissues. We confirm that synonymous codon usage differs significantly between the tissues. However, the effect is very weak: the variability of synonymous codon usage between tissues represents only 2.3% of the total codon usage variability. Moreover, this variability is directly linked to isochore-scale (>100 kb) variability of GC-content that affect both coding and introns or intergenic regions. This demonstrates that variations of synonymous codon usage between tissue-specific genes expressed in different tissues are due to regional variations of substitution patterns and not to translational selection.

Base Composition↗

Tissue-specific enhancer of the human glycoprotein hormone alpha-subunit gene: dependence on cyclic AMP-inducible elements.

We identified and characterized elements which confer tissue specificity and cyclic AMP (cAMP) responsiveness to the human glycoprotein alpha-subunit gene. An enhancer containing an 18-base-pair repeat conferred cAMP responsiveness in a non-tissue-specific fashion. DNase I protection assays revealed DNA-binding factors that bound to this element in both placental and nonplacental cells. It also enhanced the alpha-subunit promoter in a tissue-specific manner but had a negligible effect on a heterologous promoter. A unique element found upstream of this enhancer had no independent activity but, in combination with the cAMP-responsive enhancer, distinctly increased the tissue-specific activity of both the alpha-subunit promoter and a heterologous promoter. A factor that bound to this upstream element was found in placental but not nonplacental cells. We conclude that this novel element acts, perhaps through a specific trans-acting factor, in concert with a cAMP-responsive enhancer to confer tissue specificity to the alpha-subunit gene.

Animals↗

Tissue-specific protein kinase C isoform expression in rat uterine tissue.

OBJECTIVE: Activation of the phosphatidylinositol signaling pathway plays a key role during the generation of agonist-stimulated phasic myometrial contractions. Protein kinase C (PKC), a component of this signaling pathway, has been previously shown to produce feedback inhibition of agonist-stimulated myometrial contractions. The studies described in this report were performed to survey the tissue-specific expression of several PKC isoforms in the rat uterus. METHODS: Uterine tissue was obtained from timed pregnant and normally cycling adult female Sprague-Dawley rats. Immunohistochemical studies were performed using the Vectastain ABC immunostaining technique and PKC isoform-specific polyclonal antibodies. Western blot studies were performed using myometrial tissue separated into cytosol and membrane fractions by differential centrifugation. RESULTS: These studies confirmed significant expression of the PKC-alpha, -beta 2, -delta, -eta, and -zeta isoforms in myometrium from pregnant and estrus rats, whereas only trace or no expression of the PKC-beta 1, -gamma, -epsilon, and -theta isoforms was observed. Expression of the PKC-alpha, -beta 2, and -eta isoforms decreased modestly during the latter days of gestation; in contrast, PKC-delta and -zeta remained stable during this period. The immunohistochemical studies confirmed expression of the PKC-alpha, -beta 2, -delta, -eta, and -zeta isoforms in both circular and longitudinal smooth-muscle layers of the near-term pregnant rat uterus. CONCLUSION: In summary, these studies have confirmed significant levels of expression of several isoforms of PKC in estrus and near-term pregnant rat uterine tissue, which was most prominent in the smooth-muscle cells of the myometrium.

Animals↗

Tissue-specific characteristics of in vivo electric gene: transfer by tissue and intravenous injection of plasmid DNA.

PURPOSE: To evaluate the tissue-specific characteristics of electric gene transfer after tissue and intravenous injection of naked plasmid DNA (pDNA). METHODS: pDNA encoding firefly luciferase was injected directly into the liver, kidney, spleen, skin and muscle, or into the tail vein of mice, and electric pulses were then applied to one of these organs. The distribution of transgene expressing cells was evaluated using pDNA encoding beta-galactosidase. RESULTS: Tissue injection of pDNA produced a significant degree of transgene expression in any tissue with the greatest amount in the liver, followed by kidney and spleen. The expression in these organs decreased quickly with time, and muscle showed the greatest expression at 7 days. Electroporation significantly increased the expression, and the expression level was comparable among the organs. Intravenous injection of pDNA followed by electroporation resulted in a significant expression in the liver, spleen, and kidney but not in the skin or muscle. CONCLUSIONS: Electric gene transfer to the liver, kidney, and spleen can be an effective approach to obtain significant amounts of transgene expression by either tissue or intravenous injection of pDNA, whereas it is only effective after tissue injection as far as skin- or muscle-targeted gene transfer is concerned.

Animals↗

Tissue-specific distribution of carotenoids and vitamin E in tissues of newly hatched chicks from various avian species.

The aim of this study was to evaluate carotenoid and vitamin E distribution in egg and tissues of newly hatched chicks from wild mallard (Anas platyrhynchos), game pheasant (Phasianus colchicus), free-range guinea fowl (Numida meleagris), hen (Gallus domesticus) and domestic duck (Anas platyrhynchos) and intensively housed hens. Carotenoid concentrations in the egg yolk of free-range guinea fowl, pheasant and wild mallard were similar (61.3-79.2 microg/g). Egg yolks from ducks and intensively housed hens were characterised by the lowest carotenoid concentration comprising 11.2-14.8 microg/g. However, carotenoid concentration in eggs from free-range ducks and hens was less than half of that in free-range guinea fowl or pheasant. Depending on carotenoid concentration in the livers of species studied could be placed in the following descending order: free living pheasant>free-range guinea fowl>>free-range hen>>intensively housed hen>wild mallard>>housed duck>free-range duck. The carotenoid concentrations in other tissues of free-range guinea fowl and pheasant were substantially higher than in the other species studied. Egg yolk of housed hens was characterised by the highest alpha- and gamma-tocopherol concentrations. In accordance with the alpha-tocopherol concentration in the egg yolk, the birds can be placed in the following descending order: intensively housed hen>wild mallard>free-living pheasant>free-range duck>free-range hen=free-range guinea fowl>housed duck. The main finding of this work is species- and tissue-specific differences in carotenoid and vitamin E distribution in the various avian species studied.

Animals↗

Relationship between the tissue-specificity of mouse gene expression and the evolutionary origin and function of the proteins.

BACKGROUND: The combination of complete genome sequence information with expression data enables us to characterize the relationship between a protein's evolutionary origin or functional category and its expression pattern. In this study, mouse proteins were assigned into functional and phyletic groups and the gene expression patterns of the different protein groupings were examined by microarray analysis in various mouse tissues. RESULTS: Our results suggest that the proteins that are universally distributed in all tissues are predominantly enzymes and transporters. In contrast, the tissue-specific set is dominated by regulatory proteins (signal transduction and transcription factors). An increased tendency to tissue-specificity is observed for metazoan-specific proteins. As the composition of the phyletic groups highly correlates with that of the functional groups, the data were tested in order to determine which of the two factors -- function or phyletic age -- is dominant in shaping the expression profile of a protein. The observed differences in expression patterns of genes between functional groups were found mainly to reflect their different phyletic origin. The connection between tissue specificity and phyletic age cannot be explained by the recent rate of evolution. Finally, although metazoan-specific proteins tend to be tissue-specific compared with phyletically conserved proteins present in all domains of life, many such 'universal' proteins are also tissue-specific. CONCLUSION: The minimal cellular transcriptome of the metazoan cell differs from that of the ancestral unicellular eukaryote: new functions were added (metazoan-specific proteins), whilst other functions became specialized and no longer took place in all cells (tissue-specific pre-metazoan proteins).

Amino Acid Substitution↗

The effects of streptozotocin diabetes on tissue specific lipase activities in the rat.

Fasting in normal rats produced a fall in hepatic triglyceride lipase (H-TGL) activity as well as lipoprotein lipase (LPL) activities of adipose tissue and psoas minor muscle. On the other hand, LPL activities of heart and diaphragm were not decreased by fasting; the former, in fact, was increased significantly. Changes in tissue specific lipase activity caused by withdrawal of insulin from insulin-treated diabetic animals paralleled in direction the changes induced by starvation of normal rats. Furthermore, it was shown in the present paper that the tissue specific lipase activity of diabetic rats became stuck in the starve phase of the starve-feed cycle regardless of dietary intake. The changes of the tissue specific lipase activities, especially of liver, adipose tissue and heart, appeared to coincide with those of plasma insulin levels. These results strongly suggest that the tissue specific lipase system is under hormonal regulation by insulin. Streptozotocin diabetes produced hypertriglyceridemia. The possible mechanism of the hypertriglyceridemia in diabetic animals was discussed in connection with the role of the tissue specific lipase system in the serum triglyceride metabolism.

Adipose Tissue↗

RTS, a rice anther-specific gene is required for male fertility and its promoter sequence directs tissue-specific gene expression in different plant species.

A tapetum-specific gene, RTS, has been isolated by differential screening of a cDNA library from rice panicles. RTS is a unique gene in the rice genome. RNA blot analysis and in situ hybridization indicates that this gene is predominantly expressed in the anther's tapetum during meiosis and disappears before anthesis. RTS has no introns and encodes a putative polypeptide of 94 amino acids with a hydrophobic N-terminal region. The nucleotide and deduced amino acid sequence of the gene do not show significant homology to any known sequences. However, a sequence in the promoter region, GAATTTGTTA, differs only by one or two nucleotides from one of the conserved motifs in the promoter region of two pollen-specific genes of tomato. Several other sequence motifs found in other anther-specific promoters were also identified in the promoter of the RTS gene. Transgenic and antisense RNA approaches revealed that RTS gene is required for male fertility in rice. The promoter region of RTS, when fused to the Bacillus amyloliquefaciens ribonuclease gene, barnase, or the antisense of the RTS gene, is able to drive tissue-specific expression of both genes in rice, creeping bentgrass (Agrostis stolonifera L.) and Arabidopsis, conferring male sterility to the transgenic plants. Light and near-infrared confocal microscopy of cross-sections through developing flowers of male-sterile transgenics shows that tissue-specific expression of barnase or the antisense RTS genes interrupts tapetal development, resulting in deformed non-viable pollen. These results demonstrate a critical role of the RTS gene in pollen development in rice and the versatile application of the RTS gene promoter in directing anther-specific gene expression in both monocotyledonous and dicotyledonous plants, pointing to a potential for exploiting this gene and its promoter for engineering male sterility for hybrid production of various plant species.

Amino Acid Sequence↗

Two distinct TATA-less promoters direct tissue-specific expression of the rat apo-B editing catalytic polypeptide 1 gene.

The species and tissue specificity of apolipoprotein (apo) B mRNA editing is determined by the expression of apoB editing catalytic polypeptide 1 (APOBEC-1), the cytidine deaminase that catalyzes apoB mRNA editing. To understand the molecular mechanisms that regulate the transcription of APOBEC-1, we characterized rat APOBEC-1 cDNA and genomic DNA. cDNA cloning and RNase protection analysis showed two alternative promoters for the tissue-specific expression of APOBEC-1 in the liver and intestine, Pliv and Pint. Both promoters lack a TATA box, and Pint belongs to the MED-1 class of promoters, which initiate transcription at multiple sites. We also identified two allelic forms of the APOBEC-1 gene from the characterization of two rat APOBEC-1 P1 genomic clones, RE4 and RE5. The RE4 allele is 18 kilobases long and contains six exons and five introns, whereas the RE5 allele contains an additional approximately 8 kilobases of intron sequences and an extra exon encoding a 5'-untranslated region; however, the APOBEC-1 transcripts from the two alleles appear to have similar, if not identical, functions. Transgenic mouse studies showed that Pliv was preferentially used in the liver, kidney, brain, and adipose tissues, whereas Pint was preferentially used in the small intestine, stomach, and lung. Our results suggest that the tissue-specific expression of APOBEC-1 is governed by multiple regulatory elements exerting control over a single coding sequence. The presence or absence of these regulatory elements may determine the tissue-specific expression of APOBEC-1 in other mammalian species.

APOBEC-1 Deaminase↗

Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta.

The biosynthesis of estrogens from androgens is catalyzed by a enzyme of the endoplasmic reticulum termed aromatase cytochrome P-450 (P-450AROM). The gene encoding P-450AROM was isolated in our laboratory utilizing a full-length P-450AROM cDNA and a primer-extended cDNA obtained from human placental libraries as probes. We have found that the P-450AROM gene spans at least 75 kilobases and the region encoding the P-450AROM protein is comprised of nine exons. In addition, there are at least two untranslated exons, I.1 and I.2, upstream of which are found putative promoter sequences thought to be responsible for expression of P-450AROM in placenta. To determine if these promoters are utilized to regulate P-450AROM expression in adipose tissue, we have used polymerase chain reaction technology in an attempt to amplify the untranslated exons out of human adipose total RNA. The untranslated exons could not be amplified out of adipose RNA although they could be amplified out of placental RNA. When oligonucleotides corresponding to these untranslated exons were used in Northern analysis of RNA from human adipose stromal cells, no hybridizable mRNA species was detectable. Putative promoter sequences 326 and 110 base pairs (bp) upstream of the 5' end of exon II were evaluated as adipose P-450AROM promoters by primer extension analysis and S1 nuclease protection assays. Both methods suggest a start site of transcription 26 bp down-stream of the TATAAA sequence located 110 bp from the placental intron-exon II junction. These results indicate that tissue-specific regulation of aromatase activity in the human is achieved in part by the use of alternative transcriptional start sites and tissue-specific promoters.

Adipose Tissue↗