REST-VP16 activates multiple neuronal differentiation genes in human NT2 cells

被引:41
作者
Immaneni, A [1 ]
Lawinger, P [1 ]
Zhao, ZY [1 ]
Lu, WY [1 ]
Rastelli, L [1 ]
Morris, JH [1 ]
Majumder, S [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA
关键词
D O I
10.1093/nar/28.17.3403
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 RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress transcription of a battery of neuronal differentiation genes in non-neuronal cells by binding to a specific consensus DNA sequence present in their regulatory regions. However, REST/NRSF-/- mice suggest that the absence of REST/NRSF-dependent repression alone is not sufficient for the expression of these neuronal differentiation genes and that the presence of other promoter/enhancer-specific activators is required. Here we describe the construction of a recombinant transcription factor, REST-VP16, by replacing repressor domains of REST/NRSF with the activation domain of a viral activator VP16, In transient transfection experiments, REST-VP16 was found to operate through RE1 binding site/neuron-restrictive enhancer element (RE1/NRSE), activate plasmid-encoded neuronal promoters in various mammalian cell types and activate cellular REST/ NRSF target genes, even in the absence of factors that are otherwise required to activate such genes. Efficient expression of REST-VP16 through adenoviral vectors in NT2 cells, which resemble human committed neuronal progenitor cells, was found to cause activation of multiple neuronal genes that are characteristic markers for neuronal differentiation. Thus, REST-VP16 could be used as a unique tool to study neuronal differentiation pathways and neuronal diseases that arise due to the deregulation of this process.
引用
收藏
页码:3403 / 3410
页数:8
相关论文
共 41 条
[1]   CoREST:: A functional corepressor required for regulation of neural-specific gene expression [J].
Andrés, ME ;
Burger, C ;
Peral-Rubio, MJ ;
Battaglioli, E ;
Anderson, ME ;
Grimes, J ;
Dallman, J ;
Ballas, N ;
Mandel, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (17) :9873-9878
[2]   AN EFFICIENT AND FLEXIBLE SYSTEM FOR CONSTRUCTION OF ADENOVIRUS VECTORS WITH INSERTIONS OR DELETIONS IN EARLY REGION-1 AND REGION-3 [J].
BETT, AJ ;
HADDARA, W ;
PREVEC, L ;
GRAHAM, FL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (19) :8802-8806
[3]   Turning brain into blood: A hematopoietic fate adopted by adult neural stem cells in vivo [J].
Bjornson, CRR ;
Rietze, RL ;
Reynolds, BA ;
Magli, MC ;
Vescovi, AL .
SCIENCE, 1999, 283 (5401) :534-537
[4]   Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton [J].
Brunet, LJ ;
McMahon, JA ;
McMahon, AP ;
Harland, RM .
SCIENCE, 1998, 280 (5368) :1455-1457
[5]   NRSF/REST is required in vivo for repression of multiple neuronal target genes during embryogenesis [J].
Chen, ZF ;
Paquette, AJ ;
Anderson, DJ .
NATURE GENETICS, 1998, 20 (02) :136-142
[6]   REST - A MAMMALIAN SILENCER PROTEIN THAT RESTRICTS SODIUM-CHANNEL GENE-EXPRESSION TO NEURONS [J].
CHONG, JHA ;
TAPIARAMIREZ, J ;
KIM, S ;
TOLEDOARAL, JJ ;
ZHENG, YC ;
BOUTROS, MC ;
ALTSHULLER, YM ;
FROHMAN, MA ;
KRANER, SD ;
MANDEL, G .
CELL, 1995, 80 (06) :949-957
[7]   Progression from extrinsic to intrinsic signaling in cell fate specification: A view from the nervous system [J].
Edlund, T ;
Jessell, TM .
CELL, 1999, 96 (02) :211-224
[8]  
FULLER GN, 1996, PEDIAT NEOPLASIA MOR, P153
[9]   The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex [J].
Grimes, JA ;
Nielsen, SJ ;
Battaglioli, E ;
Miska, EA ;
Speh, JC ;
Berry, DL ;
Atouf, F ;
Holdener, BC ;
Mandel, G ;
Kouzarides, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (13) :9461-9467
[10]   SPECIFIC TRANSCRIPTION FACTORS STIMULATE SIMIAN-VIRUS 40 AND POLYOMAVIRUS ORIGINS OF DNA-REPLICATION [J].
GUO, ZS ;
DEPAMPHILIS, ML .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (06) :2514-2524