Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Milk protein gene expression is regulated by the synergistic interactions of several lactogenic hormones, including insulin, PRL, and glucocorticoids. Whey acidic protein (WAP) gene expression is highly dependent on glucocorticoids, and to a lesser extent than casein gene expression, on the presence of PRL. Previous studies have demonstrated that a distal DNase I hypersensitive site in the rat WAP gene 5'-flanking region containing several binding sites for nuclear factor I is required for high level WAP gene expression in transgenic mice. In this study several specific glucocorticoid receptor (GR) binding sites were identified flanking these nuclear factor I sites using an in vitro DNase I footprinting assay with baculovirus-expressed GR. These sites were able to confer dexamethasone inducibility to a heterologous thymidine kinase-chloramphenicol acetyltransferase reporter gene construct in transient cotransfection experiments with GR in CV1 cells. Administration of dexamethasone to adrenal-ectomized mice carrying the +2020 rat WAP transgene during lactation demonstrated that glucocorticoids are required to maintain transgene expression in the mammary gland. Furthermore, glucocorticoid-induced changes in transgene expression were correlated with the appearance of DNase I hypersensitive sites. These results indicate that at least part of glucocorticoid regulation of WAP gene expression is mediated through the direct interaction of GR with glucocorticoid response elements in the distal promoter region resulting in steroid hormone-dependent alterations in chromatin structure.
 ...
PMID:Glucocorticoid regulation of rat whey acidic protein gene expression involves hormone-induced alterations of chromatin structure in the distal promoter region. 785 50

Several gene constructs containing the firefly luciferase gene and the herpes simplex virus thymidine kinase gene promoter (TK) were used to evaluate the transcriptional activity of the distal enhancer (-3442, -3285) of the rabbit alphas1-casein gene. Six copies of the enhancer (6i) were added upstream of the TK-luciferase construct in the presence or absence of the chicken beta-globin 5'HS4 insulator. The activity of the constructs was tested by transient transfection in CHO cells and in rabbit primary mammary cell cultured on plastic or on floating collagen. Constructs were also tested in stably transfected mouse mammary HC11 cells. In all cell types the multimerized alphas1-casein enhancer strongly stimulated luciferase gene expression in the presence of lactogenic hormones. It was also sensitive to the extracellular matrix in rabbit primary mammary cells. The constructs were used to generate transgenic mice. The 6i TK transgenic animals expressed the luciferase gene at very low levels irrespectively of the physiological state. No preferential expression in the mammary gland was observed. Addition of 5'HS4 insulator to the 6i TK construct did not prevent silencing in most of the transgenic lines. However, two lines expressed high luciferase levels specifically in the mammary gland. Our data suggest that 6i may confer, when insulated properly, a higher and mammary-specific expression to the TK promoter.
 ...
PMID:Effect of the rabbit alphas1-casein gene distal enhancer on the expression of a reporter gene in vitro and in vivo. 1177 32