TRANSCRIPTIONAL REGULATION OF CYTOCHROME P-450 GENES

P450基因既可以单独表达，也可以结构性表达。这个 可诱导基因通常在没有AFP的情况下低水平表达 诱导剂。结构性表达的P450基因也是 发育调节的。通常情况下，P450在肝脏中缺失。 出生前的动物。分娩后立即，几个P450 基因被激活，并在几天内得到充分表达 出生。为了理解这种发育程序化的机制 基因激活，目前正在研究细胞色素P4502EI基因。病毒的上游DNA 这种基因在出生后立即去甲基化，与 它的转录激活。核转录因子HNF-I是 被发现与紧挨着CYP2EI的DNA元件结合 启动子和这种结合被认为是介导转录。核酸酶 过敏性分析表明，该基因的染色质 在出生后一天内变得敏感，表明一个因素是 与DNA结合在一起。目前尚不清楚是去甲基化还是人神经营养因子-I 结合是发育基因激活的信号。 一种辐射缺失的小鼠被发现有一个缺失的 1.2厘米摩根的DNA片段在7号染色体上。这些小鼠在一年内死亡 出生后几天因肝功能衰竭。CYP2EI基因分析 表达显示，纯合子的新生小鼠的缺失不 快递CYP2EI杂合子和纯合子正常小鼠确实会产生 细胞色素P450 2 EI m RNA。因为HNF-1基因在5号染色体上，而CYP2EI在 7号染色体，但在这些小鼠缺失区域的近端，缺乏 可能是由于一种反式作用蛋白的结合 转录因子在调控级联反应中处于上位 包括HNF-I的表达。

P450 genes are either individually or are constitutively expressed. The inducible genes are usually expressed at low levels in the absence of an inducing agent. Constitutively expressed P450 genes are also developmentally regulated. Typically P450s are absent in livers of animals prior to birth. Immediately after parturition, several P450 genes are activated and become fully expressed within a few days after birth. To understand the mechanism of this developmentally programmed gene activation, the CYP2EI gene is being studied. The upstream DNA of this gene becomes demethylated immediately after birth coincident with its transcription activation. The nuclear transcription factor HNF-I was found to bind to a DNA element immediately adjacent to the CYP2EI promoter and this binding is thought to mediate transcription. Nuclease hypersensitivity analysis indicated that the chromatin of the CYP2EI gene becomes sensitive within one day after birth suggesting that a factor is bound to the DNA. It is still unknown whether demethylation or HNF-I binding is the signal of developmental gene activation. A strain of radiation deletion mice were found that have a deletion of a 1.2 centiMorgan segment of DNA on chromosome 7. These mice die within a few days after birth due to liver failure. Analysis of CYP2EI gene expression revealed that newborn mice homozygous for the deletion do not express CYP2EI. Heterozygotes and homozygous normal mice do produce CYP2EI MRNA. Since the Hnf-1 gene is on chromosome 5, and CYP2EI is on chromosome 7, but proximal to the deleted region in these mice, the lack of CYP2EI gene expression might be due to the binding of a trans-acting transcription factor that is epistatic in the regulatory cascade that includes HNF-I expression.