Structure of the 5'-flanking region of the rat prostaglandin F(2alpha) receptor gene and its transcriptional control functions in hepatocytes.
Structure of the 5'-flanking region of the rat prostaglandin F(2alpha) receptor gene and its transcriptional control functions in hepatocytes.
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大鼠前列腺素F(2α)受体基因5侧翼区的结构及其在肝细胞中的转录控制功能。
DOI：
10.1006/bbrc.2000.3791
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发表时间：
2000
影响因子：
3.1
通讯作者：
G. Püschel
中科院分区：
文献类型：
--
作者：
F. Neuschäfer‐Rube;U. Möller;G. Püschel
前列腺素F（2 α）（PGF（2 α））通过七螺旋G（q）-偶联的PGF（2 α）-受体（FP-R）调节肝细胞功能，所述七螺旋G（q）-偶联的PGF（2 α）-受体在肝脏中仅在肝细胞中表达。本研究的目的是分离大鼠FP-R基因的5 '侧翼区，并阐明其在大鼠肝细胞中的基础和IL-6调节的转录控制功能。大鼠肝细胞FP-R mRNA的5 '非翻译区与大鼠胚胎星形胶质细胞或黄体中的相应区域不同。它由外显子1a和外显子2编码，外显子1和外显子2之间相隔1。4kb内含子，包含分别编码大鼠胚胎星形胶质细胞和黄体FP-R mRNA的5 '非翻译区的外显子1b和1c。5 '-RACE结果显示，肝细胞的转录起始位点位于起始ATG上游263 bp处。克隆并测序了覆盖rFP-R基因5 '侧翼区从转录起始位点-1至-2590bp的DNA片段。它的3 ′-三分之二与小鼠FP-R启动子有65%的序列同源性，但与牛FP-R启动子没有同源性。在重叠序列中，大多数假定的转录因子结合位点在小鼠和大鼠之间是保守的。大鼠启动子不含经典的TATA或CAAT盒，但含有转录因子C/EBP、加塔-1、HNF-1、HNF-3 β、SP-1和USF的推定结合位点。将含有部分5 '-侧翼区的荧光素酶报告基因构建体转染到大鼠肝细胞中。荧光素酶表达排名-181 >/= -608< -1418 >-1821 >/=-2590。最强的转录活性是由-608和-1418之间的区域赋予的，该区域含有一簇潜在的HNF-1和HNF-3 β结合位点，可能允许FP-R mRNA在肝细胞中的排他性表达。IL-6可降低肝细胞中FP-R mRNA的表达量和-2590启动子片段控制下的荧光素酶表达。
Prostaglandin F(2alpha) (PGF(2alpha)), modulates hepatocyte functions via a heptahelical G(q)-coupled PGF(2alpha)-receptor (FP-R) which in liver is expressed exclusively in hepatocytes. The aim of the present study was to isolate the 5'-flanking region of the rat FP-R gene and to elucidate its basal and IL-6-modulated transcription control function in rat hepatocytes. The 5'-non-translated region of the rat hepatocyte FP-R mRNA differed from the corresponding region in rat fetal astrocyte or corpus luteum. It was encoded by exons 1a and 2 which were separated by a 1. 4 kb intron containing the exons 1b and 1c coding for the 5'-untranslated region of rat fetal astrocyte and corpus luteum FP-R mRNA, respectively. The transcription initiation site in hepatocytes was localized 263 bp upstream of the start ATG by 5'-RACE. A DNA-fragment covering the 5'-flanking region of the rFP-R gene from -1 of the transcription initiation site to -2590 bp was cloned and sequenced. Its 3'-two thirds had a 65% sequence identity to the mouse FP-R promoter however no homology to the bovine FP-R promoter. In the overlapping sequence most of the putative transcription factor binding sites were conserved between mouse and rat. The rat promoter contained no classical TATA- or CAAT-boxes but putative binding sites for the transcription factors C/EBP, GATA-1, HNF-1, HNF-3beta, SP-1, and USF. Luciferase reporter gene constructs containing portions of the 5'-flanking region were transfected into rat hepatocytes. Luciferase expression ranked -181 >/= -608 < -1418 > -1821 >/= -2590. The strongest transcriptional activity was conferred by the region between -608 and -1418 containing a cluster of potential HNF-1 and HNF-3beta binding sites that might allow the exclusive expression of FP-R mRNA in hepatocytes. The amount of FP-R mRNA and the luciferase expression under control of the -2590 promoter fragment were reduced by IL-6 in hepatocytes.
影响因子：
56.9
作者：
BRIGGS, MR;KADONAGA, JT;TJIAN, R
通讯作者：
TJIAN, R
影响因子：
10.5
作者：
JOHNSON, PF;LANDSCHULZ, WH;MCKNIGHT, SL
通讯作者：
MCKNIGHT, SL
影响因子：
56.9
作者：
COURTOIS, G;MORGAN, JG;CRABTREE, GR
通讯作者：
CRABTREE, GR