Department of Genetics, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
Insect Biochem Mol Biol. 2011 Nov;41(11):863-71. doi: 10.1016/j.ibmb.2011.07.002. Epub 2011 Jul 27.
Organisms induce the expression of detoxification enzymes such as cytochrome P450s to deal with xenobiotics encountered in the environment. Research using cell culture systems has identified some of the cis-regulatory elements (CREs) and transcription factors involved in the induction of P450 genes in response to xenobiotic challenges. It was recently found that the CREs required for the basal expression of some P450s are distinct from the CREs involved in their induction. How these CREs mediate induction to xenobiotics in a tissue specific manner is not known. In this paper we show that, in Drosophila melanogaster, the induction response of the P450 gene Cyp6g1 to the xenobiotic Phenobarbital (PB) requires the presence of both tissue specific enhancers and a distinct CRE. The CRE does not drive gene expression but is required for the induction response. Site-directed mutagenesis of sequences within the CRE, sequences similar to mouse PB induction sequences, reduces the level of induction by PB, suggesting some degree of mechanistic conservation between flies and mice. This CRE may represent a unique class of CREs that has no inherent role in the basal transcriptional activity of genes, but is required for induction responses. Variations within this class of CREs may explain the variability of gene induction responses.
生物体会诱导解毒酶（如细胞色素 P450）的表达，以应对环境中遇到的外来物质。使用细胞培养系统的研究已经确定了一些顺式调控元件（CREs）和转录因子，它们参与了 P450 基因对外源物挑战的诱导。最近发现，一些 P450 基因基础表达所需的 CREs 与参与其诱导的 CREs 不同。这些 CREs 如何以组织特异性的方式介导对外源物的诱导尚不清楚。在本文中，我们表明，在黑腹果蝇中，P450 基因 Cyp6g1 对外源物苯巴比妥（PB）的诱导反应需要组织特异性增强子和一个独特的 CRE 的存在。该 CRE 不驱动基因表达，但对于诱导反应是必需的。对 CRE 内序列的定点突变，与小鼠 PB 诱导序列相似的序列，降低了 PB 的诱导水平，这表明在苍蝇和老鼠之间存在一定程度的机制保守性。这个 CRE 可能代表了一类独特的 CRE，它们在外源物诱导反应中没有固有作用，而在诱导反应中是必需的。这类 CRE 中的变异可能解释了基因诱导反应的可变性。
