Interaction of a Novel Sex-dependent, Growth Hormone-regulated Liver Nuclear Factor with CYP2C12 Promoter*
Interaction of a Novel Sex-dependent, Growth Hormone-regulated Liver Nuclear Factor with CYP2C12 Promoter*
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新型性别依赖性、生长激素调节的肝核因子与 CYP2C12 启动子的相互作用*
DOI：
10.1074/jbc.271.47.29978
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
H. Choi
中科院分区：
文献类型：
--
作者：
D. Waxman;Shuping Zhao;H. Choi
CYP 2C 12是一种类固醇羟化酶细胞色素P450，其在成年大鼠肝脏中的雌性特异性表达由成年雌性大鼠的连续血浆生长激素（GH）特征转录激活。对CYP 2C 12基因的5′侧翼进行DNase I足迹法和凝胶迁移率变动分析，以鉴定可能有助于该P450基因的GH调节的性别依赖性转录的顺式作用元件和反式作用因子。DNA酶I足迹分析显示，性别和生长激素调节的DNA酶I超敏反应位点在几个蛋白质结合位点的边界检测沿着1560个核苷酸的CYP 2C 12上游段。五个不同的网站绑定一个新的连续GH调节的核因子，GHNF，这是丰富的成年女性和连续GH处理的男性肝细胞核提取物相比，未经处理的男性肝细胞核提取物。另外两个足迹位点对应于肝转录因子C/EBP和白蛋白D元件结合蛋白的结合位点，第三个足迹位点对应于HNF 1结合位点。在成年男性特异性肝P450基因CYP 2C 11的5′-近端启动子中也发现了GHNF的特异性结合位点，这表明GHNF可能有助于连续GH下调该基因。GHNF不同于与大鼠Spi 2.1基因上游的GH应答元件结合的核因子，也不同于GH可激活的潜伏性胞质转录因子STAT 1、STAT 3和STAT 5。这些发现支持以下假设：成年雌性大鼠肝脏中持续的GH激活的CYP 2C 12转录（a）涉及一种新的GH调节的核因子的激活，该核因子与该细胞色素P450基因的5′侧翼沿着的多个位点结合，以及（B）通过与GH脉冲激活的STAT 5通路不同的信号通路进行，该信号通路被提议用于诱导CYP 2C 11和其他雄性表达的肝脏基因。
CYP2C12 is a steroid hydroxylase cytochrome P450 whose female-specific expression in adult rat liver is transcriptionally activated by the continuous plasma growth hormone (GH) profile characteristic of adult female rats. DNase I footprinting and gel mobility shift analysis of the 5′-flank of the CYP2C12 gene were carried out to identify cis-acting elements and trans-acting factors that may contribute to the GH-regulated, sex-dependent transcription of this P450 gene. DNase I footprinting analysis revealed sex- and GH-regulated DNase I hypersensitivity sites at the boundaries of several protein binding sites detected along a 1560-nucleotide upstream segment of CYP2C12. Five distinct sites bound a novel continuous GH-regulated nuclear factor, GHNF, which is enriched in adult female and continuous GH-treated male liver nuclear extracts compared to untreated male liver nuclear extracts. Two other footprinted sites correspond to binding sites for the liver transcription factors C/EBP and albumin D element-binding protein and a third to an HNF1 binding site. A specific binding site for GHNF was also found in the 5′-proximal promoter of CYP2C11, an adult male-specific liver P450 gene, suggesting that GHNF may contribute to the down-regulation of that gene by continuous GH. GHNF was distinguished from the nuclear factors that bind to a GH response element upstream of the rat Spi 2.1 gene and is also distinct from the GH-activatable latent cytoplasmic transcription factors STAT 1, STAT 3, and STAT 5. These findings support the hypothesis that continuous GH-activated transcription of CYP2C12 in adult female rat liver (a) involves the activation of a novel GH-regulated nuclear factor which binds to multiple sites along the 5′-flank of this cytochrome P450 gene, and (b) proceeds via a signaling pathway distinct from the GH pulse-activated STAT5 pathway proposed to induce CYP2C11 and other male-expressed liver genes.
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细胞色素 P450IIC 基因基础表达的转录调控元件。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Venepally,P;Chen,D;Kemper,B
通讯作者：
Kemper,B
成年大鼠肝脏中雄性特异性类固醇 6 β-羟化酶 P-450 2a（基因产物 IIIA2）的垂体调节。
DOI：
10.1210/mend-4-3-447
发表时间：
1990
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Waxman,DJ;Ram,PA;Notani,G;LeBlanc,GA;Alberta,JA;Morrissey,JJ;Sundseth,SS
通讯作者：
Sundseth,SS
DOI：
10.1073/pnas.88.9.3807
发表时间：
1991-05-01
影响因子：
11.1
作者：
XANTHOPOULOS, KG;PREZIOSO, VR;DARNELL, JE
通讯作者：
DARNELL, JE
体内生长激素治疗可快速刺激酪氨酸磷酸化和 Stat3 的激活。
DOI：
10.1210/mend.9.2.7776967
发表时间：
1995
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Gronowski,AM;Zhong,Z;Wen,Z;Thomas,MJ;DarnellJr,JE;Rotwein,P
通讯作者：
Rotwein,P
大鼠线粒体细胞色素 P-450c27/25 和生长激素诱导型丝氨酸蛋白酶抑制剂的 mRNA 5 末端区域之间的序列互补性。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shayiq,RM;Avadhani,NG
通讯作者：
Avadhani,NG