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Results for “tissue specificity”

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PubMed1993

The mitochondrial aldehyde dehydrogenase gene resides in an HTF island but is expressed in a tissue-specific manner.

The tissue distribution of mitochondrial aldehyde dehydrogenase (ALDH2) in rats was analyzed by activity assays, and by Western and Northern blotting. ALDH2 was expressed at highest levels in liver. The mRNA levels were intermediate in the kidney and lung, while lower levels were found in spleen and heart. The transcript was undetectable in other tissues tested. The human ALDH2 5' flanking region (-200 to +60) contains similar numbers of CpG and GpC dinucleotides and the rat ALDH2 gene was undermethylated in liver, kidney, and spleen. This suggests that the ALDH2 promoter resides in a Hpa II tiny fragment (HTF) island, unlike most genes expressed in a tissue-specific manner.

Aldehyde Dehydrogenase↗

PubMed1994

Human multiple tissue western blots: a new immunological tool for the analysis of tissue-specific protein expression.

Human multiple tissue Western (MTW) blots are premade immunoblots prepared using proteins isolated from adult human tissue. The proteins are isolated from whole tissue homogenates under conditions designed to minimize proteolysis and to ensure maximal representation of tissue-specific proteins. Sodium dodecyl sulfate (SDS) solubilized proteins are fractionated by SDS polyacrylamide gel electrophoresis and electroblotted onto polyvinylidene fluoride membranes to generate blots ready for incubation with researcher-supplied antibodies. Each lane of an MTW blot contains an equivalent amount of total protein, allowing for the analysis of tissue-specific expression of a particular protein(s). The utility of MTW blots for Western blot applications was demonstrated by the detection of various cytoskeletal proteins and members of the annexin family of calcium-dependent, membrane-binding proteins. Several of these antigens were detected in separate cycles of antibody incubations using the same MTW blot. This approach is possible using a stripping procedure that allows the researcher to selectively remove both primary and secondary antibodies in a single incubation. The ease of multiple reprobings makes MTW blots both economical and convenient research tools for Western blot analyses of human tissue-specific proteins.

Adult↗

PubMed1993

Distinct nuclear proteins competing for an overlapping sequence of cyclic adenosine monophosphate and negative regulatory elements regulate tissue-specific mouse renin gene expression.

The mouse renin locus (Ren-1d) exhibits specific patterns of tissue expression. It is expressed in kidney but not submandibular gland (SMG). This locus contains a negative regulatory element (NRE) and a cAMP responsive element (CRE) that share an overlapping sequence. In the kidney, CRE binding proteins (CREB) and NRE binding proteins (NREB) compete for binding to this sequence, with the CREB having a greater affinity. In the SMG, CREB is inactivated by an inhibitory protein, permitting NREB to bind to the sequence, thus inhibiting Ren-1d expression. We hypothesize that the competition between NREB and CREB for this sequence governs tissue-specific expression of mouse renin. We speculate that this may be a general paradigm that determines tissue-specific gene expression.

Animals↗

PubMed2005

Faithful expression of living color reporter genes in transgenic medaka under two tissue-specific zebrafish promoters.

To test tissue specificity of zebrafish gene promoters in a heterologous fish species, two transgenic medaka lines under two zebrafish promoters were generated. Under the zebrafish skeletal muscle-specific mylz2 promoter, transgenic medaka expressed green fluorescent protein (GFP) exclusively in skeletal muscles, mimicking the endogenous medaka mylz2 mRNA expression and also identical to GFP expression in mylz2:gfp transgenic zebrafish. A madaka mylz2 promoter was also capable of directing skeletal muscle-specific GFP expression in transient transgenic zebrafish embryos. In the krt8:rfp transgenic medaka line with the zebrafish epithelial krt8 promoter, red fluorescent protein was specifically expressed in the skin epithelia as well as the epithelial lining cells of the anterior digestive tract, which was also identical to GFP expression in krt8:gfp transgenic zebrafish. Therefore, the two zebrafish promoters faithfully function in a heterologous fish species, and it is likely that the mechanisms of tissue-specific expression are largely conserved among fish species.

Amino Acid Sequence↗

PubMed1999

Human prostate-specific transglutaminase gene: promoter cloning, tissue-specific expression, and down-regulation in metastatic prostate cancer.

OBJECTIVES: To investigate the tissue-specific and differential expression of the human prostate-specific transglutaminase (pTGase) gene in metastatic prostate cancer (CaP) and to study how this gene is regulated in the prostate. METHODS: Northern blot hybridization and polymerase chain reaction (PCR) were performed using RNA from a variety of organs to confirm prostate-specific expression of the gene. Relative quantitative reverse transcriptase-PCR (RT-PCR) was performed to investigate the differential expression of the gene among normal prostates and prostates with CaP and metastatic CaP. The pTGase gene promoter was cloned using genomic library screening and sequencing. Transfection experiments and chloramphenicol acetyltransferase (CAT) assays were performed to study the regulation of the gene. RESULTS: Northern hybridization and RT-PCR confirmed that the gene is only expressed in the prostate. Relative quantitative RT-PCR demonstrated a loss of expression of the pTGase gene among men with CaP and higher Gleason grades. In metastatic CaP tissue from various sites, 86% of the samples lost expression of the gene. We cloned and sequenced a 1.4-kilobase promoter region of the pTGase gene. Transfection and CAT assay results supported the theory that certain elements in the -1 to -520 region are sufficient to direct prostate-specific expression of the gene. Additional elements in the -520 to -1400 region may also contribute to its prostate-specific expression. CONCLUSIONS: The results of our study demonstrate that the human pTGase gene is only expressed in prostate tissue and that its expression is inhibited in most metastatic CaP. Prostate-specific expression of the gene is controlled by elements in the promoter region. The observed preferential loss of pTGase gene expression in metastatic CaP may be important to the pathogenesis and progression of this disease.

Base Sequence↗

PubMed1994

Isolation of two isoforms of the PAX3 gene transcripts and their tissue-specific alternative expression in human adult tissues.

We have isolated two isoforms of cDNA clones from the human PAX3 gene, a candidate gene responsible for Waardenburg syndrome type I (WSI) as well as a gene associated with development of alveolar rhabdomyosarcoma. The gene product is considered to be one of transcription factors, and the two cDNA clones isolated, termed PAX3A and PAX3B, were generated by alternative splicing. The transcripts coded 215 and 206 amino acids, respectively, and shared 196 amino acids at the NH2 end. The amino acid sequence in the common region (residues 1-196) showed a 100% identity with that of exons 1-4 of the mouse Pax-3 gene. However, both of the PAX3 cDNAs lacked the DNA sequence corresponding to the paired-type homeodomain of the mouse Pax-3 gene. Analysis of gene expression in human adult tissues by reverse transcriptase polymerase chain reaction (RT-PCR) revealed tissue-specific expression of this gene. PAX3B was expressed in most of the tissues examined, but the PAX3A type of transcript was detected only in the cerebellum, esophagus, and skeletal muscle.

Adult↗

PubMed1984

Avian scale development. X. Dermal induction of tissue-specific keratins in extraembryonic ectoderm.

Epidermal-dermal tissue interactions regulate morphogenesis and tissue-specific keratinization of avian skin appendages. The morphogenesis of scutate scales differs from that of reticulate scales, and the keratin polypeptides of their epidermal surfaces are also different. Do the inductive cues which initiate morphogenesis of these scales also establish the tissue-specific keratin patterns of the epidermis, or does the control of tissue-specific keratinization occur at later stages of development? Unlike feathers, scutate and reticulate scales can be easily separated into their epidermal and dermal components late in development when the major events of morphogenesis have been completed and keratinization will begin. Using a common responding tissue (chorionic epithelium) in combination with scutate and reticulate scale dermises, we find that these embryonic dermises, which have completed morphogeneis, can direct tissue-specific stratification and keratinization. In other words, once a scale dermis has acquired its form, through normal morphogenesis, it is no longer able to initiate morphogenesis of that scale, but it can direct tissue-specific stratification and keratinization of a foreign ectodermal epithelium, which itself has not undergone scale morphogenesis.

Animals↗

PubMed2005

Promoter features related to tissue specificity as measured by Shannon entropy.

BACKGROUND: The regulatory mechanisms underlying tissue specificity are a crucial part of the development and maintenance of multicellular organisms. A genome-wide analysis of promoters in the context of gene-expression patterns in tissue surveys provides a means of identifying the general principles for these mechanisms. RESULTS: We introduce a definition of tissue specificity based on Shannon entropy to rank human genes according to their overall tissue specificity and by their specificity to particular tissues. We apply our definition to microarray-based and expressed sequence tag (EST)-based expression data for human genes and use similar data for mouse genes to validate our results. We show that most genes show statistically significant tissue-dependent variations in expression level. We find that the most tissue-specific genes typically have a TATA box, no CpG island, and often code for extracellular proteins. As expected, CpG islands are found in most of the least tissue-specific genes, which often code for proteins located in the nucleus or mitochondrion. The class of genes with no CpG island or TATA box are the most common mid-specificity genes and commonly code for proteins located in a membrane. Sp1 was found to be a weak indicator of less-specific expression. YY1 binding sites, either as initiators or as downstream sites, were strongly associated with the least-specific genes. CONCLUSIONS: We have begun to understand the components of promoters that distinguish tissue-specific from ubiquitous genes, to identify associations that can predict the broad class of gene expression from sequence data alone.

Animals↗

PubMed2004

Testis-specific TAF homologs collaborate to control a tissue-specific transcription program.

Alternate forms of the PolII transcription initiation machinery have been proposed to play a role in selective activation of cell-type-specific gene expression programs during cellular differentiation. The cannonball (can) gene of Drosophila encodes a homolog of a TBP-associated factor (dTAF5) protein expressed only in spermatocytes, where it is required for normal transcription of genes required for spermatid differentiation. We show that Drosophila primary spermatocytes also express four additional tissue-specific TAFs: nht (homolog of dTAF4), mia (homolog of dTAF6), sa (homolog of dTAF8) and rye (homolog of dTAF12). Mutations in nht, mia and sa have similar effects in primary spermatocytes on transcription of several target genes involved in spermatid differentiation, and cause the same phenotypes as mutations in can, blocking both meiotic cell cycle progression and spermatid differentiation. The nht, mia, sa and rye proteins contain histone fold domain dimerization motifs. The nht and rye proteins interact structurally when co-expressed in bacteria, similarly to their generally expressed homologs TAF4 and TAF12, which heterodimerize. Strikingly, the structural interaction is tissue specific: nht did not interact with dTAF12 and dTAF4 did not interact with rye in a bacterial co-expression assay. We propose that the products of the five Drosophila genes encoding testis TAF homologs collaborate in an alternative TAF-containing protein complex to regulate a testis-specific gene expression program in primary spermatocytes required for terminal differentiation of male germ cells.

Amino Acid Motifs↗

PubMed1991

A quantitative genetic analysis of tissue-specific catalase activity in Mus musculus.

Tissue-specific catalase activity in 3-week-old animals from inbred mouse strains 129/ReJ, BALB/c, C3H/HeAnl/Cas-1b, C3H/HeSnJ, C3H/S, C57BL/6J, and Swiss-Webster was found to be highly variable by analysis of variance (P = 0.01). Appropriate crosses were made among strains which were classified as normal (BALB/c, C3H/HeSnJ, C3H/S), hypocatalasemic (129/ReJ, C57BL/6J), and acatalasemic (C3H/HeAnl/Cas-1b) with respect to blood catalase activity to study the inheritance of the blood, kidney, liver, and lung catalase activity levels in a number of generations (reciprocal F1's, F2, two backcrosses--BC1 and BC2--and some RI lines). Segregation analysis and statistical methods which tested different models of inheritance as well as calculations of heritability were used in an effort to assess and evaluate genetic parameters that affect catalase activity. Results indicate that the inheritance of blood catalase activity in the cross involving acatalasemic and normal (BALB/c, C3H/HeSnJ) strains is compatible with the single-locus difference between the parental strains; however, the difference between the acatalasemic and the hypocatalasemic strain (C57BL/6J) would require additional genetic interaction for a satisfactory explanation. A similar pattern of generalization also applies to the inheritance of kidney catalase activity. The segregation pattern for the liver and lung catalase activity in most crosses is significantly different from the expectations of the single locus model. These results are compatible with the concept that a number of genes must affect tissue-specific catalase activity in mice. These may include previously described (e.g., Ce-1 and Ce-2) or novel genetic regulators/modifiers which interact with a single structural gene (Cas-1) or its product to produce the catalase phenotype characteristic of specific tissues in each strain.

Acatalasia↗

PubMed2001

Identification of a tissue-specific putative transcription factor in breast tissue by serological screening of a breast cancer library.

Application of SEREX (serological analysis of recombinant tumor cDNA expression libraries) to different tumor types has led to the identification of several categories of human tumor antigens. In this study, the analysis of a breast cancer library with autologous patient serum led to the isolation of seven genes, designated NY-BR-1 through NY-BR-7. NY-BR-1, representing 6 of 14 clones isolated, showed tissue-restricted mRNA expression in breast and testis but not in 13 other normal tissues tested. Among tumor specimens, NY-BR-1 mRNA expression was found in 21 of 25 breast cancers but in only 2 of 82 nonmammary tumors. Structural analysis of NY-BR-1 cDNA and the corresponding genomic sequences in the recently released working draft of human genome indicated that NY-BR-1 is composed of 37 exons and has an open reading frame of 4.0-4.2 kb, encoding a peptide of Mr 150,000-160,000. A bipartite nuclear localization signal motif indicates a nuclear site for NY-BR-1, and the presence of a bZIP site (DNA-binding site followed by leucine zipper motif) suggests that NY-BR-1 is a transcription factor. Additional structural features include five tandem ankyrin repeats, implying a role for NY-BR-1 in protein-protein interactions. NY-BR-1 thus represents a breast tissue-specific putative transcription factor with autoimmunogenicity in breast cancer patients. In addition to NY-BR-1, a homologous gene, NY-BR-1.1, was identified in this study. NY-BR-1.1 shares 54% amino acid homology with NY-BR-1 and also shows tissue-restricted mRNA expression. However, unlike NY-BR-1, NY-BR-1.1 mRNA is expressed in brain, in addition to breast and testis. The exon structure of NY-BR-1.1 remains to be defined. Using human genome database, NY-BR-1 was localized to chromosome 10p11-p12, and NY-BR-1.1 was tentatively localized to chromosome 9.

Alternative Splicing↗

PubMed1989

A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter.

A rat thyroglobulin promoter fragment, capable of directing thyroid-specific transcription, binds at least three different factors, TTF-1, TTF-2 and UFA, which are all present in nuclear extracts of the differentiated rat thyroid cell line FRTL-5. TTF-1 and TTF-2 are FRTL-5 specific, as demonstrated by their absence in nuclear extracts prepared from cell lines that do not express any thyroid-differentiated function, while UFA is present in all cell lines tested. TTF-1 has been extensively purified. It binds to the rat thyroglobulin promoter at three different sites which share sequence homology. Mutations in two of the three sites decrease both binding of TTF-1 in vitro and promoter function in vivo. This suggests that the tissue-specific expression of the thyroglobulin genes is mediated, at least in part, by the presence of a transcription factor exclusively in thyroid cells.

Animals↗

PubMed2002

Genome-wide detection of tissue-specific alternative splicing in the human transcriptome.

We have developed an automated method for discovering tissue-specific regulation of alternative splicing through a genome-wide analysis of expressed sequence tags (ESTs). Using this approach, we have identified 667 tissue-specific alternative splice forms of human genes. We validated our muscle-specific and brain-specific splice forms for known genes. A high fraction (8/10) were reported to have a matching tissue specificity by independent studies in the published literature. The number of tissue-specific alternative splice forms is highest in brain, while eye-retina, muscle, skin, testis and lymph have the greatest enrichment of tissue-specific splicing. Overall, 10-30% of human alternatively spliced genes in our data show evidence of tissue-specific splice forms. Seventy-eight percent of our tissue-specific alternative splices appear to be novel discoveries. We present bioinformatics analysis of several tissue-specific splice forms, including automated protein isoform sequence and domain prediction, showing how our data can provide valuable insights into gene function in different tissues. For example, we have discovered a novel kidney-specific alternative splice form of the WNK1 gene, which appears to specifically disrupt its N-terminal kinase domain and may play a role in PHAII hypertension. Our database greatly expands knowledge of tissue-specific alternative splicing and provides a comprehensive dataset for investigating its functional roles and regulation in different human tissues.

Alternative Splicing↗

PubMed1992

Immune response: tissue specific T-lymphocytes.

The lymphatic system forms a 'blind' plexus of vessels that in general are found in tissue which has an inherently high replicative capacity. It is this system that is responsible for the rapid deployment and circulation of tissue-specific T-lymphocytes for the inspection of cell-surface aberrations within the tissue. The presence of tissue-specific T-lymphocytes explains why 90% of lymphocytes are found outside the lymphatic system and why they migrate in a selective manner. The tissue-specific T-lymphocyte is considered to express a common lymphocyte cell surface pattern, the homotype, and a tissue-specific cell-surface pattern, the histotype which may involve MHCA and mHCA. It is the histotypic pattern that is responsible for the tissue specificity of the tissue-specific T-lymphocyte. The presence of tissue-specific T-lymphocytes does pose problems for the immune system. If different tissue-specific T-lymphocytes met within a particular tissue, 'lost' lymphocytes, an immune response will be generated against the intruder (lost lymphocyte), and the intruder will not be able to recruit other immunocompetent cells in that tissue. This immune reaction is an attempt to change the histotypic pattern of the intruder. This situation would explain the autologous immune response. This response however is suppressed in the systemic system by immunosuppressive compounds from the liver. It is only in the tissues that the tissue-specific T-lymphocytes are released from this suppression, in order to initiate immune reactions against aberrant cell-surface patterns.

Animals↗

PubMed1996

Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles.

An expression profile of active genes in a human neuroblastoma cell line CHP134 was obtained by collecting 1222 partial sequences from a 3'-directed cDNA library representing a non-biased mRNA population. By comparing this expression profile with the compiled profiles of multiple tissues, several novel gene transcripts that appeared only in the profile of the neuroblastoma cell line were identified. Further analyses by Northern blotting revealed two specific cDNA clones that are expressed in most of the human neuroblastomas examined, and three that are in some of the human neuroblastoma cell lines as well as in the adult human brain. Full-size cDNAs were cloned using these five partial cDNA sequences as probes and sequenced. A database search revealed that they are all novel and unique sequences: one sharing some amino acid sequence similarities with a cytoskeletal protein, two clones likely to be transcriptional factors, a clone that has characteristic potassium channel properties, and a clone that is non-homologous to any one of the known proteins. Thus, we argue that the collection of 3'-directed cDNA sequences in combination with the compiled expression profiles of active genes in multiple tissues is a powerful tool for discovering novel genes that are specifically expressed in a given cell or tissue, in this case neuroblastomas and/or nerve tissue.

Amino Acid Sequence↗

PubMed2004

Genetic relationship among gill-infecting Myxobolus species (Myxosporea) of cyprinids: molecular evidence of importance of tissue-specificity.

The importance of tissue-specificity was studied in Myxobolus spp. infecting the gills of 7 cyprinid species. The 18S rDNA of 10 Myxobolus species was amplified by optimised nested-PCR, resulting in approximately 1600 bp PCR products. Phylogenetic trees generated by distance matrix and parsimony analyses revealed 4 main groups. Muscle-infecting species all belonged to the same group, while members of 2 gill-infecting groups were clearly distinguishable on the basis of tissue-specificity, and were also recognisable by differences in spore morphology. On the basis of tissue tropism, phylogenetic relationships among the species examined indicate that genetic separation is a more ancient evolutionary feature than host-specificity.

Animals↗

PubMed1989

Tissue-specific determinants of human atrial natriuretic factor gene expression in cardiac tissue.

Elements controlling tissue-specific expression of the human atrial natriuretic factor gene have been examined in primary cultures of neonatal rat cardiocytes. When a 68-base pair fragment from human atrial natriuretic factor (hANF) 5'-flanking sequence (positions -400 to -333) was placed upstream from the herpes simplex thymidine kinase promoter linked to a bacterial reporter gene (chloramphenicol acetyltransferase), a tissue-specific positive regulatory effect was observed in atrial as well as ventricular cardiocytes but not in nonmyocardial cells. The cis-acting element in this fragment was orientation- and position-dependent. Examination of nuclear protein extracts for the presence of factors capable of interacting with the 5'-flanking sequence of the hANF gene revealed a cardiocyte-specific factor which bound to the 68-base pair fragment. This association was both tissue- and sequence-specific. These findings indicate that a cis-acting element present in the proximal 5'-flanking sequence confers tissue-specific expression upon the hANF gene, possibly through association with a cardiac-specific nuclear protein.

Atrial Natriuretic Factor↗

PubMedDate not supplied

Tissue-specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury.

Several reports imply that bone marrow hematopoietic stem cells transdifferentiate into tissue-specific stem cells; however, the possibility of committed tissue-specific stem cells pre-existing in the bone marrow has not been dealt with adequately. We present here an alternative explanation of the so-called phenomenon of stem cell transdifferentiation. First, we postulate that tissue-committed stem/progenitor cells circulate in the peripheral blood and compete for tissue-specific niches. The circulation of these cells plays an important physiological role in maintaining a pool of stem cells in distant parts of the body and the number of these cells in peripheral blood can be increased by the administration of agents similar to those used for mobilization of hematopoietic stem cells. Second, we postulate that bone marrow tissue is a source of various stem-cell chemoattractants and survival factors and provides an environment that chemoattracts tissue-specific circulating stem/progenitor cells. In this context, we envision bone marrow as a "home" or "hide-out place" not only of hematopoietic stem cells but also of already differentiated circulating tissue-specific stem/progenitors. In support of this concept, we report here that mRNA of several early markers for muscle (Myf-5, Myo-D), neural (GFAP, nestin) and liver (CK19, fetoprotein) is detectable in circulating (adherent cell-depleted) peripheral blood mononuclear cells. Moreover, using real-time RT-PCR, we found that the level of expression of these markers increases in the peripheral blood of humans and mice after mobilization by G-CSF. Furthermore, using stromal-derived factor-1 (SDF-1) chemotaxis and real-time RT-PCR analysis, we present evidence that early tissue-specific stem cells reside in normal human and murine bone marrow, express the CXCR4 receptor on their surface and can be highly enriched (in humans and mice) after chemotaxis to SDF-1 gradient. All our experiments were performed on freshly isolated cells to exclude the potential contribution of transdifferentiated hematopoietic stem or mesenchymal cells in the culture. We maintain that any transdifferentiation studies employing populations of bone marrow cells should rule out the possibility that the apparently pure hematopoietic stem cell population could in fact contain pre-existing tissue-specific stem/progenitors.

Animals↗