CCAAT displacement protein (CDP/cut) recognizes a silencer element within the lactoferrin gene promoter

被引:53
作者
KhannaGupta, A
Zibello, T
Kolla, S
Neufeld, EJ
Berliner, N
机构
[1] YALE UNIV,SCH MED,DEPT INTERNAL MED,SECT HEMATOL,NEW HAVEN,CT 06510
[2] CHILDRENS HOSP,BOSTON,MA 02115
[3] HARVARD UNIV,SCH MED,BOSTON,MA 02115
关键词
D O I
10.1182/blood.V90.7.2784.2784_2784_2795
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Expression of neutrophil secondary granule protein (SGP) genes is coordinately regulated at the transcriptional level, and is disrupted in specific granule deficiency and leukemia. We analyzed the regulation of SGP gene expression by luciferase reporter gene assays using the lactoferrin (LF) promoter. Reporter plasmids were transiently transfected into non-Lf-expressing hematopoietic cell lines. Luciferase activity was detected from reporter plasmids containing basepair (bp) -387 to bp -726 of the LF promoter, but not in a -916-bp plasmid. Transfection of a -916-bp plasmid into a LF-expressing cell line resulted in abrogation of the silencing effect. Sequence analysis of this region revealed three eight-bp repetitive elements, the deletion of which restored wildtype levels of luciferase activity to the -916-bp reporter plasmid. Electrophoretic mobility shift assay and UV cross-linking analysis identified a protein of approximately 180 kD that binds to this region in non-Lf-expressing cells but not in LF-expressing cells, This protein was identified to be the CCAAT displacement protein (CDP/cut). CDP/cut has been shown to downregulate expression of gp91-phox, a gene expressed relatively early in the myeloid lineage. Our observations suggest that the binding of CDP/cut to the LF silencer element serves to suppress basal promoter activity of the LF gene in non-if-expressing cells. Furthermore, overexpression of CDP/cut in cultured myeloid stem cells blocks LF expression upon granulocyte colony-stimulating factor-induced neutrophil maturation without blocking phenotypic maturation. This block in LF expression may be due, in part, to the persistence of CDP/cut binding to the LF silencer element. (C) 1997 by The American Society of Hematology.
引用
收藏
页码:2784 / 2795
页数:12
相关论文
共 58 条
[1]   A NEW BIPARTITE DNA-BINDING DOMAIN - COOPERATIVE INTERACTION BETWEEN THE CUT REPEAT AND HOMEO DOMAIN OF THE CUT HOMEO PROTEINS [J].
ANDRES, V ;
CHIARA, MD ;
MAHDAVI, V .
GENES & DEVELOPMENT, 1994, 8 (02) :245-257
[2]  
ANDRES V, 1992, DEVELOPMENT, V116, P324
[3]   SEQUENCE-SPECIFIC DNA-BINDING OF INDIVIDUAL CUT REPEATS OF THE HUMAN CCAAT DISPLACEMENT/CUT HOMEODOMAIN PROTEIN [J].
AUFIERO, B ;
NEUFELD, EJ ;
ORKIN, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7757-7761
[4]   ACTIVITY OF 2 DIFFERENT SILENCER ELEMENTS OF THE CHICKEN LYSOZYME GENE CAN BE COMPENSATED BY ENHANCER ELEMENTS [J].
BANIAHMAD, A ;
MULLER, M ;
STEINER, C ;
RENKAWITZ, R .
EMBO JOURNAL, 1987, 6 (08) :2297-2303
[5]   MUTUALLY EXCLUSIVE INTERACTION OF THE CCAAT-BINDING FACTOR AND OF A DISPLACEMENT PROTEIN WITH OVERLAPPING SEQUENCES OF A HISTONE GENE PROMOTER [J].
BARBERIS, A ;
SUPERTIFURGA, G ;
BUSSLINGER, M .
CELL, 1987, 50 (03) :347-359
[6]   THE PROTEIN ID - A NEGATIVE REGULATOR OF HELIX-LOOP-HELIX DNA-BINDING PROTEINS [J].
BENEZRA, R ;
DAVIS, RL ;
LOCKSHON, D ;
TURNER, DL ;
WEINTRAUB, H .
CELL, 1990, 61 (01) :49-59
[7]   DIFFERENTIATION REQUIRES CONTINUOUS ACTIVE CONTROL [J].
BLAU, HM .
ANNUAL REVIEW OF BIOCHEMISTRY, 1992, 61 :1213-1230
[8]   PRIMARY STRUCTURE AND EXPRESSION OF A PRODUCT FROM CUT, A LOCUS INVOLVED IN SPECIFYING SENSORY ORGAN IDENTITY IN DROSOPHILA [J].
BLOCHLINGER, K ;
BODMER, R ;
JACK, J ;
JAN, LY ;
JAN, YN .
NATURE, 1988, 333 (6174) :629-635
[9]   Dna binding by cut homeodomain proteins is down-modulated by protein kinase C [J].
Coqueret, O ;
Berube, G ;
Nepveu, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (40) :24862-24868
[10]   REPRESSION VERSUS ACTIVATION IN THE CONTROL OF GENE-TRANSCRIPTION [J].
COWELL, IG .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (01) :38-42