Transcriptional regulation of the hamster Muc1 gene: identification of a putative negative regulatory element.
Transcriptional regulation of the hamster Muc1 gene: identification of a putative negative regulatory element.
复制标题
仓鼠 Muc1 基因的转录调控：假定负调控元件的鉴定。
DOI：
10.1152/ajplung.00342.2000
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Kim,KChul
中科院分区：
文献类型：
--
作者：
Lee,InsongJames;Hyun,SangWon;Nandi,Asit;Kim,KChul
粘蛋白基因Muc 1在腺上皮细胞中表达，并参与润滑和保护功能。它也在许多癌中过表达，包括乳腺癌和肺癌细胞。为了研究Muc 1的转录调控，我们克隆了一个包含仓鼠Muc 1基因启动子区域的2.4 kb片段，并分析了其介导转录的能力。转录起始定位于TATA盒下游的22个碱基对。我们使用缺失/报告基因构建体对仓鼠（HP-1和中国仓鼠卵巢）和人细胞（MCF-7、A549和BEAS-2B）中的Muc 1启动子进行了功能分析。在-555和-252之间的正调控区和-1，652和-1，614之间的负调控元件（P-NRE）在转染细胞中被发现是活跃的。P-NRE含有一个Yin Yang 1（YY 1）转录因子结合位点，用HP-1细胞核提取物进行的电泳迁移率变动分析显示YY 1与该位点结合。我们的数据表明YY 1可能在Muc 1基因的转录中起抑制作用。
The mucin geneMuc1is expressed in glandular epithelial cells and is involved in lubricative and protective functions. It is also overexpressed in many carcinomas including breast and lung cancer cells. To study the transcriptional regulation ofMuc1, we cloned a 2.4-kb fragment containing the promoter region of the hamsterMuc1gene and analyzed it for its ability to mediate transcription. Transcriptional initiation was localized to 22 base pairs downstream of the TATA box. We performed functional analysis of theMuc1promoter in hamster (HP-1 and Chinese hamster ovary) and human cells (MCF-7, A549, and BEAS-2B) using deletion/reporter constructs. A positive regulatory region between bases −555 and −252 and a putative negative regulatory element (P-NRE) between nucleotides −1,652 and −1,614 were found to be active in transfected cells. The P-NRE contains a yin yang 1 (YY1) transcription factor binding site, and electrophoretic mobility shift assays with HP-1 cell nuclear extract revealed the binding of YY1 to this site. Our data suggest that YY1 may play an inhibitory role in the transcription of theMuc1gene.