CIRCADIAN TRANSCRIPTION OF THE CHOLESTEROL 7-ALPHA HYDROXYLASE GENE MAY INVOLVE THE LIVER-ENRICHED BZIP PROTEIN DBP
CIRCADIAN TRANSCRIPTION OF THE CHOLESTEROL 7-ALPHA HYDROXYLASE GENE MAY INVOLVE THE LIVER-ENRICHED BZIP PROTEIN DBP
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DOI：
10.1101/gad.7.10.1871
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发表时间：
1993-10-01
影响因子：
10.5
通讯作者：
SCHIBLER, U
中科院分区：
文献类型：
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作者：
LAVERY, DJ;SCHIBLER, U
富肝转录因子DBP的表达具有严格的昼夜节律。我们提供的证据表明，DBP是大鼠编码胆固醇7 α羟化酶（C7alphaH）基因的昼夜节律表达的调节器，C7alphaH是胆固醇转化为胆汁酸的限速酶。与DBP一样，C7alphaH mRNA在晚上达到峰值水平，其循环与日常食物和光线线索无关。正如对DBP靶基因的预测，C7alphaH昼夜节律表达的初级水平是在转录水平。在共转染实验中，DBP可以通过位于-225附近的同源DNA位点激活C7alphaH启动子。与传统技术相比，通过一种新方法制备的核提取物可以获得DBP和其他非组蛋白的近定量恢复，DBP激活所需的DNA位点是核因子在C7alphaH启动子上占据的主要位点。在这个位点，主要的结合活性是夜间特异性复合物，DBP是其组成部分。这些数据表明DBP可能通过胆固醇7 - α羟化酶的昼夜转录调节在胆固醇稳态中发挥重要作用。
The liver-enriched transcription factor DBP is expressed with a stringent circadian rhythm. We present evidence that DBP is a regulator of the circadian expression of the rat gene encoding cholesterol 7alpha hydroxylase (C7alphaH), the rate-limiting enzyme in the conversion of cholesterol to bile acids. As with DBP, C7alphaH mRNA reaches peak levels in the evening, and its cycling is independent of daily food and light cues. As predicted for a DBP target gene, the primary level of C7alphaH circadian expression is at the transcriptional level. DBP can activate the C7alphaH promoter in cotransfection assays through a cognate DNA site centered around -225. In nuclear extracts prepared by a novel method that, in contrast to conventional techniques, yields near-quantitative recovery of DBP and other non-histone proteins, the DNA site required for DBP activation is the predominant site of occupancy by nuclear factors on the C7alphaH promoter. At this site, the predominant binding activity is an evening-specific complex of which DBP is a component. These data suggest that DBP may play an important role in cholesterol homeostasis through circadian transcriptional regulation of cholesterol 7alpha hydroxylase.