DEFINITION OF A GC-RICH MOTIF AS REGULATORY SEQUENCE OF THE HUMAN IL-3 GENE - COORDINATE REGULATION OF THE IL-3 GENE BY CLE2/GC BOX OF THE GM-CSF GENE IN T-CELL ACTIVATION

被引:37
作者
NISHIDA, J
YOSHIDA, M
ARAI, K
YOKOTA, T
机构
[1] DNAX RES INST MOLEC & CELLULAR BIOL INC,DEPT MOLEC BIOL,901 CALIF AVE,PALO ALTO,CA 94304
[2] UNIV TOKYO,INST MED SCI,DEPT CELLULAR & MOLEC BIOL,MINATO KU,TOKYO 108,JAPAN
[3] UNIV TOKYO,INST MED SCI,DEPT MOLEC & DEV BIOL,MINATO KU,TOKYO 108,JAPAN
关键词
SIGNAL TRANSDUCTION; DNA BINDING PROTEIN; NF-GM2;
D O I
10.1093/intimm/3.3.245
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The human IL-3 gene, located on chromosome 5, contains several cis-acting DNA sequences, i.e. CLE (conserved lymphokine element) and a GC-rich region, similar to the GM-CSF gene. To investigate the role of these elements, the 5' flanking region of the IL-3 gene was attached to a bacterial chloramphenicol acetyltransferase (CAT) gene. The fusion plasmids were analyzed by an in vitro transcription system using Jurkat cell nuclear extract prepared from cells stimulated with phorbol-12-myristate-13-acetate and calcium ionophore (PMA/A23187), introduced into Jurkat cells, expressed transiently, and stimulated by co-transfection of human T cell leukemia virus type I (HTLV-I) encoded transactivator, p40tax. The GC-rich region enhanced TATA-dependent transcription in the in vitro transcription system and also strongly responded to p40tax stimulation in the in vivo cotransfection assay. Using this GC-rich region as a probe, we identified a constitutive DNA-protein complex, alpha, whose binding specificity correlates with transcription activity. However, this element is not sufficient for the expression of the IL-3 gene in response to T cell activation signals (PMA/A23187) and no sequence was found within the IL-3 gene which mediates the response to PMA/A23187. The enhancer sequence which responds to T cell activation signals may be located outside the IL-3 gene and may be shared by other lymphokines, possibly by GM-CSF. We propose that the GM-CSF enhancer (CLE2/GC box) which mediates the response to T cell activation signals may stimulate the expression of the IL-3 gene.
引用
收藏
页码:245 / 254
页数:10
相关论文
共 35 条
[1]  
ARAI N, 1989, VECTORS TOOLS STUDY, P255
[2]   CLOSE GENETIC AND PHYSICAL LINKAGE BETWEEN THE MURINE HEMATOPOIETIC GROWTH-FACTOR GENES GM-CSF AND MULTI-CSF (IL3) [J].
BARLOW, DP ;
BUCAN, M ;
LEHRACH, H ;
HOGAN, BIM ;
GOUGH, NM .
EMBO JOURNAL, 1987, 6 (03) :617-623
[3]  
BICKEL M, 1988, EXP HEMATOL, V16, P691
[4]  
BICKEL M, 1989, J CELL BIOCHEM S, V13, P34
[5]   CLONING AND NUCLEOTIDE-SEQUENCE OF THE MURINE INTERLEUKIN-3 GENE [J].
CAMPBELL, HD ;
YMER, S ;
FUNG, MC ;
YOUNG, IG .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1985, 150 (02) :297-304
[6]   THE ROLE OF HELPER T-CELL PRODUCTS IN MOUSE B-CELL DIFFERENTIATION AND ISOTYPE REGULATION [J].
COFFMAN, RL ;
SEYMOUR, BWP ;
LEBMAN, DA ;
HIRAKI, DD ;
CHRISTIANSEN, JA ;
SHRADER, B ;
CHERWINSKI, HM ;
SAVELKOUL, HFJ ;
FINKELMAN, FD ;
BOND, MW ;
MOSMANN, TR .
IMMUNOLOGICAL REVIEWS, 1988, 102 :5-28
[7]   REGULATION OF THE HUMAN INTERLEUKIN-2 RECEPTOR ALPHA-CHAIN PROMOTER - ACTIVATION OF A NONFUNCTIONAL PROMOTER BY THE TRANSACTIVATOR GENE OF HTLV-1 [J].
CROSS, SL ;
FEINBERG, MB ;
WOLF, JB ;
HOLBROOK, NJ ;
WONGSTAAL, F ;
LEONARD, WJ .
CELL, 1987, 49 (01) :47-56
[8]   FIREFLY LUCIFERASE GENE - STRUCTURE AND EXPRESSION IN MAMMALIAN-CELLS [J].
DEWET, JR ;
WOOD, KV ;
DELUCA, M ;
HELINSKI, DR ;
SUBRAMANI, S .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (02) :725-737
[9]   ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI [J].
DIGNAM, JD ;
LEBOVITZ, RM ;
ROEDER, RG .
NUCLEIC ACIDS RESEARCH, 1983, 11 (05) :1475-1489
[10]   CONTROL OF EUKARYOTIC MESSENGER-RNA SYNTHESIS BY SEQUENCE-SPECIFIC DNA-BINDING PROTEINS [J].
DYNAN, WS ;
TJIAN, R .
NATURE, 1985, 316 (6031) :774-778