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Biomedical subjects

W Schmid

Publications and source records attributed to W Schmid.

At least 109 records · Page 6Linked to original sources

Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene.

Two glucocorticoid response elements (GREs) located 2.5 kb upstream of the transcription initiation site of the tyrosine aminotransferase gene were identified by gene transfer experiments and shown to bind to purified glucocorticoid receptor. Although the proximal GRE has no inherent capacity by itself to stimulate transcription, when present in conjunction with the distal GRE, this element synergistically enhances glucocorticoid induction of gene expression. Cooperativity of the two GREs is maintained when they are transposed upstream of a heterologous promoter. An oligonucleotide of 22 bp representing the distal GRE is sufficient to confer glucocorticoid inducibility. As evidenced by the mapping of DNAase I hypersensitive sites, local alterations in the structure of chromatin at the GREs take place as a consequence of hormonal treatment.

Base Sequence↗

Glucocorticoid induction of the rat tryptophan oxygenase gene is mediated by two widely separated glucocorticoid-responsive elements.

Transcription of the gene coding for tryptophan oxygenase (TO) in rat liver is induced 10-fold by glucocorticoids. To identify DNA elements mediating the glucocorticoid-regulated expression of the TO gene we transfected mouse L cells with a fusion gene consisting of 1.95 kb TO 5'-flanking sequences linked to the coding sequence of the gene for chloramphenicol acetyltransferase (CAT). CAT assay and RNA mapping experiments demonstrate that both transient and stable expression of the TO-CAT fusion gene are inducible by dexamethasone. Analysis of transcripts from 5'-deletion mutants identifies two glucocorticoid-responsive elements (GRE), located 450 bp and 1.2 kb upstream of the cap site. The purified rat glucocorticoid receptor binds to the sequence of each GRE as evidenced from footprinting experiments. Interestingly the protected sequence of the proximal footprint is by itself not sufficient for sequence induction, but requires sequences located immediately upstream.

Adrenalectomy↗

Medical genetics.

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Chorionic Villi↗

Glucocorticoid responsiveness of the transcriptional enhancer of Moloney murine sarcoma virus.

The long terminal repeat of Moloney Murine Sarcoma Virus (MoMSV) contains an imperfect direct repeat that serves as a strong transcriptional enhancer. The strength of the MoMSV enhancer is strongly dependent on the presence of glucocorticoid hormone. Mapping studies in combination with DNAase I footprinting experiments define the presence of glucocorticoid regulatory elements at the promoter-proximal ends of each enhancer repeat. These elements behave like inducible enhancers: their regulatory activity is independent of position and orientation when they are linked in cis to a heterologous promoter. These data demonstrate the modular nature of the MoMSV enhancer and identify the glucocorticoid receptor as one of the trans-acting factors that interact with the MoMSV enhancer and mediate its transcriptional activity.

Animals↗

X-linked dominant hypophosphatemia is closely linked to DNA markers DXS41 and DXS43 at Xp22.

Two families with X-linked dominant hypophosphatemia (McKusick No. *30780) were investigated for linkage of the disease locus with several marker genes defined by cloned, single-copy DNA sequences derived from defined regions of the X chromosome. Close linkage was found with DNA markers DXS41 (p99-6) and DXS43 (pD2) at Xp22, suggesting a location of the HPDR gene on the distal short arm of the X chromosome.

Chromosome Mapping↗

[Status of prenatal diagnosis in Switzerland].

In Swiss laboratories of Basel, Berne, Geneva, Lausanne, Locarno and Zurich 19'872 prenatal diagnosis were carried out from 1971 to 1983. The frequency of the tests carried out for the different indications and the numbers of the detected anomalies are presented. In 12'485 tests performed because of advanced maternal age (35 years and older) 241 chromosome anomalies were diagnosed with 125 trisomies 21 among them. In contrast, only 7 trisomies 21 were found in 5'225 samples from women below 35 years. Prevention of Down's syndrome was the prevalent motivation of 93 percent of the pregnant women. Approx. 42 percent of the Swiss women, 35 years and older, requested an amniocentesis in the course of the last few years. Remarkable progress was made in the ultrasound diagnosis of fetal malformations. Developments in the field of first trimester prenatal diagnosis and in the use of DNA technology for the diagnosis of monogenic defects are dealt with.

Adult↗

Deletions near the albino locus on chromosome 7 of the mouse affect the level of tyrosine aminotransferase mRNA.

Overlapping chromosomal deletions at the albino locus on chromosome 7 of the mouse affect the expression of several liver enzymes, including tyrosine aminotransferase (TAT; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5). With cloned TAT DNA the integrity of the TAT structural gene and its expression and inducibility by glucocorticoids and cAMP were examined in deletion homozygous mice. No difference in the structure of the gene between normal and mutant mice was detected by Southern blotting. Severely reduced amounts of TAT mRNA were detected in homozygous mutants. The residual mRNA levels could not be modulated by glucocorticoids or cAMP. We conclude that a trans-acting control function required for expression and inducibility of mouse TAT can be assigned to the chromosomal region near the albino locus.

Animals↗