Differential tissue distribution, developmental programming, estrogen regulation and promoter characteristics of cyp19 genes in teleost fish
Differential tissue distribution, developmental programming, estrogen regulation and promoter characteristics of cyp19 genes in teleost fish
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DOI：
10.1016/s0960-0760(01)00147-9
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发表时间：
2001-12-01
影响因子：
4.1
通讯作者：
Wood, E
中科院分区：
文献类型：
--
作者：
Callard, GV;Tchoudakova, AV;Wood, E
硬骨鱼的特点是，与其他脊椎动物的大脑或同一种鱼的卵巢相比，大脑雌激素生物合成水平异常高。金鱼（Carassius auratus）和斑马鱼（Danio rerio）作为了解夸张的神经雌激素生物合成的分子基础和功能意义的互补模型具有实用性。来自不同基因座（cyp 19 a和cyp 19 B）的多种细胞色素P450芳香酶（P450 arom）cDNA在脑（P450 arom B A）和卵巢（P450 arom A>> B）中差异表达，并具有不同的发育程序（B A）和对雌激素上调的反应（仅B）。如通过增加的P450 aromB mRNA所测量的，功能性雌激素应答系统在受精后24-48小时（hpf）首次被检测到，与雌激素受体（ER）表达（α、β和γ）的开始一致。cyp 19 b基因的5 ′侧翼区有一个TATA盒、两个雌激素反应元件（ERE）、一个ERE半位点（ERE 1/2）、一个神经生长因子诱导-B蛋白（NGFI-B）/Nur 77反应元件（NBRE）结合。位点，以及与斑马鱼加塔-2基因神经特异性增强子相同的序列。cyp 19 a启动子区具有TATA和CAAT盒、类固醇生成因子-I（SF-1）结合位点和两个芳烃受体（AhR）/AhR核转位因子（ARNT）结合基序。这两个基因都有多个潜在的SRY/SOX结合位点（cyp 19 b和cyp 19 a分别有16个和8个）。荧光素酶报告基因在GH 3细胞中具有基础启动子活性，但差异（a >> B）与鱼垂体相反（B a）。当显微注射到受精的斑马鱼卵中时，cyp 19 b启动子驱动的绿色荧光蛋白（GFP）报告基因（而不是cyp 19 a）在30-48 hpf胚胎的神经元中表达，最显著的是在视网膜神经节细胞（RGC）及其向视顶盖的投射中。需要进一步的研究，以确定功能相关的顺式元件和细胞因子，并确定雌激素在神经发育中的调节作用。(C)2002爱思唯尔科技有限公司版权所有。
Teleost fish are characterized by exceptionally high levels of brain estrogen biosynthesis when compared to the brains of other vertebrates or to the ovaries of the same fish. Goldfish (Carassius auratus) and zebrafish (Danio rerio) have utility as complementary models for understanding the molecular basis and functional significance of exaggerated neural estrogen biosynthesis. Multiple cytochrome P450 aromatase (P450arom) cDNAs that derive from separate gene loci (cyp19a and cyp19b) are differentially expressed in brain (P450aromB >> A) and ovary (P450aromA >> B) and have a different developmental program (B >> A) and response to estrogen upregulation (B only). As measured by increased P450aromB mRNA, a functional estrogen response system is first detected 24-48 h post-fertilization (hpf), consistent with the onset of estrogen receptor (ER) expression (alpha, beta, and gamma). The 5'-flanking region of the cyp19b gene has a TATA box, two estrogen response elements (EREs), an ERE half-site (ERE1/2), a nerve growth factor inducible-B protein (NGFI-B)/Nur77 responsive element (NBRE) binding., site, and a sequence identical to the zebrafish GATA-2 gene neural specific enhancer. The cyp19a promoter region has TATA and CAAT boxes, a steroidogenic factor-I (SF-1) binding site, and two aryl hydrocarbon receptor (AhR)/AhR nuclear translocator factor (ARNT) binding motifs. Both genes have multiple potential SRY/SOX binding sites (16 and 8 in cyp19b and cyp19a, respectively). Luciferase reporters have basal promoter activity in GH3 cells, but differences (a >> b) are opposite to fish pituitary (b >> a). When microinjected into fertilized zebrafish eggs, a cyp19b promoter-driven green fluorescent protein (GFP) reporter (but not cyp19a) is expressed in neurons of 30-48 hpf embryos, most prominently in retinal ganglion cells (RGCs) and their projections to optic tectum. Further studies are required to identify functionally relevant cis-elements and cellular factors, and to determine the regulatory role of estrogen in neurodevelopment. (C) 2002 Elsevier Science Ltd. All rights reserved.