Chen Wenling, Chiang John Y L
Department of Biochemistry and Molecular Pathology, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272, USA.
Gene. 2003 Aug 14;313:71-82. doi: 10.1016/s0378-1119(03)00631-0.
Mitochondrial sterol 27-hydroxylase (CYP27A1) catalyses sterol side-chain oxidation of bile acid synthesis from cholesterol, and the first reaction of the acidic bile acid biosynthetic pathway. Hydrophobic bile acids suppress human CYP27A1 gene reporter activity when assayed in human hepatocellular blastoma HepG2 cells. Bile acids also inhibit CYP27A1 reporter activity in human embryonic kidney 293 cells. A putative bile acid response element (BARE) was mapped to a region downstream of nt -147 of the human CYP27A1 gene, within which a binding site for a liver-specific nuclear receptor, HNF4alpha, is identified. HNF4alpha strongly stimulates CYP27A1 gene transcription and mutation of its binding site markedly reduced promoter activity. Results suggest that human CYP27A1 gene transcription is suppressed by bile acids and HNF4alpha plays a pivotal role in transcriptional regulation of this gene.
线粒体固醇27-羟化酶（CYP27A1）催化从胆固醇合成胆汁酸的固醇侧链氧化反应，这是酸性胆汁酸生物合成途径的第一步反应。在人肝细胞瘤HepG2细胞中进行检测时，疏水性胆汁酸会抑制人CYP27A1基因报告基因活性。胆汁酸在人胚肾293细胞中也会抑制CYP27A1报告基因活性。一个假定的胆汁酸反应元件（BARE）被定位到人CYP27A1基因nt -147下游的一个区域，在该区域内鉴定出了肝脏特异性核受体HNF4α的一个结合位点。HNF4α强烈刺激CYP27A1基因转录，其结合位点的突变显著降低了启动子活性。结果表明，胆汁酸抑制人CYP27A1基因转录，而HNF4α在该基因的转录调控中起关键作用。
