Structure and chromosomal assignment of the sterol 12alpha-hydroxylase gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid of introns.
Structure and chromosomal assignment of the sterol 12alpha-hydroxylase gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid of introns.
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人和小鼠甾醇 12α-羟化酶基因 (CYP8B1) 的结构和染色体分配：缺乏内含子的真核细胞色素 P-450 基因。
作者：
Mats Gåfvels;M. Olin;B. P. Chowdhary;T. Raudsepp;U. Andersson;Bengt Persson;Monica Jansson;Ingemar Björkhem;Gösta Eggertsen
甾醇12 α-羟化酶（CYP 8B 1）是一种肝细胞色素P-450，控制胆汁中胆酸与鹅去氧胆酸的比例，从而控制胆固醇的溶解度。克隆了人和小鼠CYP 8B 1互补DNA和基因，并进行了结构表征。令人惊讶的是，发现这两个物种的基因组DNA都缺乏内含子。人基因的主要转录本估计为3950 bp，推定的启动子区估计为至少1360 bp。发现鼠结构基因跨越约3 kb。通过使用FISH和辐射杂交定位技术，人CYP 8B 1基因定位于染色体3p21.3-p22，而FISH将鼠对应物定位于染色体9 qF 4，该区域与第三条人类染色体同源。染色体定位和Southern杂交结果表明该基因以单拷贝存在。小鼠和人CYP 8B 1基因的转录分别从位于共有TATA盒下游51和35个碱基的位置开始。小鼠和人的启动子区的21%的同源性可能指示转录调控的差异。尽管在小鼠饥饿后观察到CYP 8B 1 mRNA的有效诱导，但通过分析潜在顺式作用元件的启动子并没有揭示这种作用背后的机制。在人启动子中，几个可能的顺式作用区域被鉴定，但它们中没有一个可以直接与胆汁酸代谢相关。用人编码区转染COS细胞后，鉴定了12 α-羟化酶的mRNA和酶活性。这是第一个哺乳动物细胞色素P-450基因报告缺乏内含子。这种结构特征的进化和基因调控的重要性进行了讨论。
Sterol 12alpha-hydroxylase (CYP8B1) is a hepatic cytochrome P-450 that controls the ratio of cholic acid over chenodeoxycholic acid in bile and thus controls the solubility of cholesterol. Both the human and the mouse CYP8B1 complementary DNA and gene were cloned and structurally characterized. Surprisingly, the genomic DNA from both species was found to lack introns. The major transcript of the human gene was estimated to be 3950 bp, and the putative promoter region was estimated to be at least 1360 bp. The murine structural gene was found to span approximately 3 kb. By using FISH and radiation hybrid mapping techniques, the human CYP8B1 gene was located to chromosome 3p21.3-p22, whereas FISH mapped the murine counterpart to chromosome 9qF4, a region that is homologous to the third human chromosome. The results from the chromosome mapping and Southern blotting indicated that the gene is present in a single copy. Transcription of the mouse and human CYP8B1 genes was initiated from a position situated 51 and 35 bases, respectively, downstream of a consensus TATA box. A homology of 21% for the promoter regions of mouse and human may indicate differences in transcriptional regulation. Although a potent induction of CYP8B1 mRNA was observed upon starvation of mice, the mechanism behind this effect was not revealed by analysis of the promoter for potential cis-acting elements. In the human promoter, several possible cis-acting regions were identified but none of them could be directly related to bile acid metabolism. After transfection of COS cells with the human coding region, mRNA and enzymatic activity for the 12alpha-hydroxylase were identified. This is the first mammalian cytochrome P-450 gene reported to lack introns. The importance of this structural feature for evolution and gene regulation is discussed.
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其中一个因素可识别 α1-抗胰蛋白酶和运甲状腺素蛋白基因中的肝脏特异性增强子。
DOI：
10.1126/science.3257586
发表时间：
1988
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Grayson,DR;Costa,RH;Xanthopoulos,KG;Darnell,JE
通讯作者：
Darnell,JE
转录启动子定位于细胞色素 P-450c27/25 基因的第二个外显子内，用于表达主要物种的两千碱基 mRNA。
影响因子：
2.9
作者：
Mullick,J;Addya,S;Sucharov,C;Avadhani,NG
通讯作者：
Avadhani,NG
影响因子：
56.9
作者：
LICHTER, P;TANG, CJC;WARD, DC
通讯作者：
WARD, DC
DOI：
10.1073/pnas.92.26.12495
发表时间：
1995-12-19
影响因子：
11.1
作者：
Long, MY;Rosenberg, C;Gilbert, W
通讯作者：
Gilbert, W
影响因子：
14.9
作者：
KORB, M;KE, YB;JOHNSON, LF
通讯作者：
JOHNSON, LF