Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of two putative, cis-acting thyroid hormone-responsive elements, TRE1 and TRE2, located at -129 to -149 and -102 to -120, respectively, on the murine alpha-myosin heavy chain (MHC) gene, has been investigated in transgenic mice. These motifs are present in a 4.5-kilobase fragment lying upstream of the transcriptional start site of the mouse alpha-MHC gene: this fragment directs appropriate expression of a reporter gene in transgenic mice (Subramaniam, A., Jones, W. K., Gulick, J., Wert, S., Neumann, J., and Robbins, J. (1991) J. Biol. Chem. 266, 24613-24620). Here, we independently mutate the TRE1 and TRE2 elements by base substitution. The mice were analyzed for transgene expression in different muscle and non-muscle tissues including the atria and ventricles. Normal levels of transgene expression were observed in euthyroid mice carrying a mutation in TRE1. In contrast to these results, mice in which TRE2 was mutated showed reduced levels of CAT activity in both the atria and ventricles, suggesting a previously undefined role for this element in the constitutive up-regulation of the alpha-MHC gene. In hypothyroid mice carrying either of these mutations, the complete cessation of ventricular expression of the chloramphenicol acetyltransferase transcripts that takes place in the alpha-5.5 (wild type) animals did not occur.
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PMID:Transgenic analysis of the thyroid-responsive elements in the alpha-cardiac myosin heavy chain gene promoter. 844 Jul 18

The increased type 1 iodothyronine deiodinase expression in hyperthyroid patients increases the fraction of plasma T3 generated from T4 by the propylthiouracil-sensitive pathway. In this study, we extend our analysis of the thyroid hormone response elements (TREs) in the 5' flanking region of the human dio1 gene. The 5' TRE (TRE2), a direct repeat separated by 4 bp (DR+4) at -660 bp, arises from an A to G substitution in an Alu sequence, the first example of this phenomenon. An SP1 binding site immediately 5' to TRE2 increases basal expression of a 430-bp dio1 promoter-chloramphenicol acetyltransferase construct in the presence of unliganded thyroid hormone receptor, thus decreasing T3 responsiveness, but does not do so when this complex is placed in its more 5' wild-type location. The two octameric binding sites of TRE1, a retinoid X-receptor independent DR+10 structure at -90, can be exchanged or inverted without loss of T3 response potency, despite significant changes in thyroid hormone receptor binding, as assessed by gel shift assays. However, the retinoic acid response of the 716-bp dio1 5' flanking region is unaffected by elimination of TRE2 but is lost with mutations in TRE1. These findings indicate the importance of functional analyses of potential ligand-responsive transcription factors, as well as the influence of position, on TRE function and interaction with basal transcription factors. The unusual features of these TREs emphasize the need to consider alternatives to canonical half-site arrangements of receptor binding sites and contexts in the evaluation of T3- and retinoic acid-responsive genes.
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PMID:Further characterization of thyroid hormone response elements in the human type 1 iodothyronine deiodinase gene. 949 50