Transcriptional regulation of human MUC4 gene: identification of a novel inhibitory element and its nuclear binding protein

doi:10.1007/s11033-013-2591-6

科研成果详情

题名	Transcriptional regulation of human MUC4 gene: identification of a novel inhibitory element and its nuclear binding protein
作者	Zhang, Jing-Jing 1,2; Zhu, Yi 1,2; Zhang, Xiong-Fei3; Liang, Wen-Biao 4; Xie, Kun-Ling 5; Tao, Jin-Qiu 5; Peng, Yun-Peng 5; Xu, Ze-Kuan 1,2; Miao, Yi 1,2
发表日期	2013-08
发表期刊	MOLECULAR BIOLOGY REPORTS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	MUC4 Gene expression Down-regulation Transcription factors Yin yang 1
其他关键词	PANCREATIC-CANCER CELLS ; EXPRESSION ; YY1 ; PROMOTER ; ADENOCARCINOMA ; METHYLATION ; REPRESSION ; YIN-YANG-1 ; GROWTH ; LINES
摘要	The human mucin 4 (MUC4) is aberrantly expressed in pancreatic adenocarcinoma and tumor cell lines, while remaining undetectable in normal pancreas, indicating its important role in pancreatic cancer development. Although its transcriptional regulation has been investigated in considerable detail, some important elements remain unknown. The aim of the present study was to demonstrate the existence of a novel inhibitory element in the MUC4 promoter and characterize some of its binding proteins. By luciferase reporter assay, we located the inhibitory element between nucleotides -2530 and -2521 in the MUC4 promoter using a series of deletion and mutant reporter constructs. Electrophoretic mobility shift assay (EMSA) with Bxpc-3 cell nuclear extracts revealed that one protein or protein complex bind to this element. The proteins binding to this element were purified and identified as Yin Yang 1 (YY1) by mass spectrometry. Supershift assay and chromatin immunoprecipitation (ChIP) assay confirmed that YY1 binds to this element in vitro and in vivo. Moreover, transient YY1 overexpression significantly inhibited MUC4 promoter activity and endogenous MUC4 protein expression. In conclusion, we reported here a novel inhibitory element in the human MUC4 promoter. This provides additional data on MUC4 gene regulation and indicates that YY1 may be a potential target for abnormal MUC4 expression.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81001079, 30972912, 81101802]; Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [Y2110310]; Science and Technology Project of Wenzhou City [Y20100243]
出版者	SPRINGER
出版地	DORDRECHT
ISSN	0301-4851
EISSN	0301-4851
卷号	40 期号:8 页码:4913-4920
DOI	10.1007/s11033-013-2591-6
页数	8
WOS类目	Biochemistry & Molecular Biology
WOS研究方向	Biochemistry & Molecular Biology
WOS记录号	WOS:000322392300029
收录类别	SCIE ; SCOPUS
URL	查看原文
PubMed ID	23813057
SCOPUSEID	2-s2.0-84881159835
通讯作者地址	[Xu, Ze-Kuan]Department of General Surgery,First Affiliated Hospital of Nanjing Medical University,300 Guangzhou Road,China
Scopus学科分类	Molecular Biology;Genetics
引用统计	被引频次：9[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/8040
专题	基础医学院（机能实验教学中心）_生物科学系_生物化学与分子生物学
通讯作者	Xu, Ze-Kuan
作者单位	1.Department of General Surgery,First Affiliated Hospital of Nanjing Medical University,300 Guangzhou Road,China; 2.Jiangsu Province Academy of Clinical Medicine,Institute of Tumor Biology,300 Guangzhou Road,China; 3.Department of Biochemistry,Wenzhou Medical College,China; 4.Transfusion Laboratory,Jiangsu Province Blood Center,China; 5.First School of Clinical Medicine,Nanjing Medical University,140 Hanzhong Road,China
推荐引用方式 GB/T 7714	Zhang, Jing-Jing,Zhu, Yi,Zhang, Xiong-Fei,et al. Transcriptional regulation of human MUC4 gene: identification of a novel inhibitory element and its nuclear binding protein[J]. MOLECULAR BIOLOGY REPORTS,2013,40(8):4913-4920.
APA	Zhang, Jing-Jing., Zhu, Yi., Zhang, Xiong-Fei., Liang, Wen-Biao., Xie, Kun-Ling., ... & Miao, Yi. (2013). Transcriptional regulation of human MUC4 gene: identification of a novel inhibitory element and its nuclear binding protein. MOLECULAR BIOLOGY REPORTS, 40(8), 4913-4920.
MLA	Zhang, Jing-Jing,et al."Transcriptional regulation of human MUC4 gene: identification of a novel inhibitory element and its nuclear binding protein".MOLECULAR BIOLOGY REPORTS 40.8(2013):4913-4920.