NRSF plays a regulatory role in human insulin gene transcription

被引:0
作者
Liu Qing-Bin [1 ]
Li Yan-Hua [1 ]
Yang Yin-Xiang [1 ]
Yuan Hong-Feng [1 ]
Zhang Rui [1 ]
Qin Li-Peng [1 ]
Lu Yang [1 ]
Zhang Sai-Nan [1 ]
Sun Di-Jin [1 ]
Chen Lin [1 ]
Bai Ci-Xian [1 ]
Nan Xue [1 ]
Wang Yun-Fang [1 ]
Pei Xue-Tao [1 ]
机构
[1] Beijing Inst Transfus Med, Lab Stem Cell Biol & Regenerat Med, Beijing 100850, Peoples R China
关键词
neuronal restrictive silencer factor (NRSF); neuronal restrictive silencer element (NRSE); insulin; promoter;
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The transcriptional repressor REI silencer transcription factor (NRSF/REST) is an important factor that restricts some neuronal traits in neurons. Since these traits are also present in pancreatic islet cells, NRSF-regulated genes involved in islet function are searched. A NRSE-like motif was analysed in human insulin promoter. The role of NRSE was evaluated by generating a model of insulin-secreting cells that firmly express NRSF. The presence of NRSF led to a decrease in activity of human insulin promoter by stable or transient transfection with human insulin-promoter luciferase. The predicted NRSE-like motif also confers NRSF-dependent transcriptional repression in the context of a surrogate gene promoter. Specific binding activity of NRSF/REST to the NRSE-like motif was confirmed by EMSA. Moreover, the binding activity is competed by consensus NRSE sequence. These data showed that human insulin promoter is regulated by the transcriptional repressor NRSF/REST via the NRSE-like motif.
引用
收藏
页码:952 / 959
页数:8
相关论文
共 15 条
[1]   Coordinate dual-gene transgenesis by lentiviral vectors carrying synthetic bidirectional promoters [J].
Amendola, M ;
Venneri, MA ;
Biffi, A ;
Vigna, E ;
Naldini, L .
NATURE BIOTECHNOLOGY, 2005, 23 (01) :108-116
[2]   Expression of neuronal traits in pancreatic beta cells - Implication of neuron-restrictive silencing factor/repressor element silencing transcription factor, a neuron-restrictive silencer [J].
Atouf, F ;
Czernichow, P ;
Scharfmann, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (03) :1929-1934
[3]   Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes [J].
Bruce, AW ;
Donaldson, IJ ;
Wood, IC ;
Yerbury, SA ;
Sadowski, MI ;
Chapman, M ;
Göttgens, B ;
Buckley, NJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (28) :10458-10463
[4]   DIFFERENTIAL EXPRESSION OF THE 2 NONALLELIC PROINSULIN GENES IN THE DEVELOPING MOUSE EMBRYO [J].
DELTOUR, L ;
LEDUQUE, P ;
BLUME, N ;
MADSEN, O ;
DUBOIS, P ;
JAMI, J ;
BUCCHINI, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (02) :527-531
[5]   INSULIN-II GENE-EXPRESSION IN RAT CENTRAL-NERVOUS-SYSTEM [J].
DEVASKAR, SU ;
SINGH, BS ;
CARNAGHI, LR ;
RAJAKUMAR, PA ;
GIDDINGS, SJ .
REGULATORY PEPTIDES, 1993, 48 (1-2) :55-63
[6]   Regulation of Pax4 paired homeodomain gene by neuron-restrictive silencer factor [J].
Kemp, DM ;
Lin, JC ;
Habener, JF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (37) :35057-35062
[7]   Neuron-restrictive silencer factor (NRSF) functions as a repressor in neuronal cells to regulate the μ opioid receptor gene [J].
Kim, CS ;
Hwang, CK ;
Choi, HS ;
Song, KY ;
Law, PY ;
Wei, LN ;
Loh, HH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (45) :46464-46473
[8]   NEURON-SPECIFIC EXPRESSION OF THE RAT-BRAIN TYPE-II SODIUM-CHANNEL GENE IS DIRECTED BY UPSTREAM REGULATORY ELEMENTS [J].
MAUE, RA ;
KRANER, SD ;
GOODMAN, RH ;
MANDEL, G .
NEURON, 1990, 4 (02) :223-231
[9]   A CELL TYPE-PREFERRED SILENCER ELEMENT THAT CONTROLS THE NEURAL-SPECIFIC EXPRESSION OF THE SCG10 GENE [J].
MORI, N ;
STEIN, R ;
SIGMUND, O ;
ANDERSON, DJ .
NEURON, 1990, 4 (04) :583-594
[10]   Comparative genomics modeling of the NRSF/REST repressor network: From single conserved sites to genome-wide repertoire [J].
Mortazavi, Ali ;
Thompson, Evonne Chen Leeper ;
Garcia, Sarah T. ;
Myers, Richard M. ;
Wold, Barbara .
GENOME RESEARCH, 2006, 16 (10) :1208-1221