Detail Eukaryotic transcriptional regulation: Studies on the expression of drug metabolizing enzymes and a tissue-specific general transcription factor Bibliografi Author: Lee, Sang Hyun ; DeJong, Jeff (Advisor) Topik: BIOLOGY; MOLECULAR|HEALTH SCIENCES; PHARMACOLOGY Bahasa: (EN )    ISBN: 0-599-81600-7     Penerbit: THE UNIVERSITY OF TEXAS AT DALLAS     Tahun Terbit: 2000     Jenis: Theses - Dissertation Fulltext: 9975914.pdf (0.0B; 1 download) Abstract Humans are constantly exposed to foreign chemical compounds. In general, these compounds are metabolized and removed from the body in a two-step process: Phase I (functionalization) and Phase II (conjugation). Phase I reactions are mainly catalyzed by cytochrome P450 (CYP) superfamily genes. Expression of these enzymes is sometimes transcriptionally induced by the chemical compounds. One example of this phenomenon is the upregulation of CYP2B1 and 2B2 gene expression by phenobarbital (PB). In this case, the basal level of gene expression of CYP2B1 and 2B2 is very low prior to Phenobarbital induction. Related to this observation, part of this dissertation describes a cis-acting regulatory element in the CYP2B1/2 promoters that has a dual specificity for the transcriptional activator NF-κB and the transcriptional repressor RBP-Jκ. I have demonstrated that when this cis-acting element is placed in front of a heterologous promoter, it repressed transcription in a manner that is dependent upon RBP-Jκ overexpression. Therefore, this element acts as a repressor binding site. In addition, I have characterized the genomic structure of human microsomal glutathione S-transferase I (mGST-I) gene, the product of which is involved in Phase II drug metabolism. Overall, the mGST-I gene spans over 18 kb of genomic DNA and is composed of four exons (I, II, III, and IV). I have also identified several alternative splicing variants of mGST-I. These variants are formed by the alternative usage of several different exon I sequences (Ia, Ib, Ic, and Id). I have also investigated the changes in gene expression caused by PB in rat liver using differential display and suppression subtractive hybridization. The results demonstrate that PB affects the expression of many different genes and also highlight the potential importance of CYP2C6 as an alternative PB-inducible model system. Finally, I undertook a preliminary characterization of TATA element binding protein (TBP)-dependent factors in rat testis, including the identification of the transcription factor IIA α/β (TFIIAα/β) and TFIIA-like-factor (ALF), a testis specific isoform of TFIIAα/β. In these studies I detected TFIIA and another TBP-dependent activity whose identity is unknown. In addition, I have identified a polypeptide in rat testis extracts that is specifically recognized by ALF antisera. In conclusion, I have investigated two different aspects of eukaryotic gene expression. One aspect is focused on a specific group of inducible drug metabolizing genes. The other aspect is concentrated on the study of a testis-specific general transcription factor. Opini Anda Klik untuk menuliskan opini Anda tentang koleksi ini! Lihat Sejarah Pengadaan  Konversi Metadata   Kembali

Copyright © 2006, 2007 Unika Atma Jaya, all rights reserved