THE INVOLVEMENT OF DEMETHYLATION IN THE MYELOID-SPECIFIC FUNCTION OF THE MOUSE M-IYSOZYME GENE DOWNSTREAM ENHANCER

被引:29
作者
KLAGES, S [1 ]
MOLLERS, B [1 ]
RENKAWITZ, R [1 ]
机构
[1] MAX PLANCK INST BIOCHEM,GENZENTRUM,W-8033 MARTINSRIED,GERMANY
关键词
D O I
10.1093/nar/20.8.1925
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
Lysozyme gene expression is a specific marker for the macrophage/granulocyte lineage of hematopoietic differentiation in mammals, its expression being gradually increased during maturation. Analysis of the mechanisms regulating mouse M lysozyme gene expression during myeloid differentiation revealed a complicated pattern of DNase I hypersensitive sites (HS sites) within the flanking regions of the gene. The HS-3 site, located in the 3'-flanking region of the gene, overlapped with an enhancer element, which is the only strong enhancer identified in the vicinity of the gene. We demonstrate a positive correlation between undermethylation of the entire 3'-flanking region, the appearance of the HS-3 site, and M lysozyme gene expression during in vitro differentiation of hematopoietic stem cells. We furthermore show that methylation of a single CpG site within the enhancer core element, only observed in immature macrophage cells in vivo, is sufficient to inhibit nuclear factor binding to this element in vitro and to inhibit its transactivation potential in DNA transfection experiments.
引用
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页码:1925 / 1932
页数:8
相关论文
共 35 条
[1]   COOPERATIVE INTERACTION OF CHICKEN LYSOZYME ENHANCER SUB-DOMAINS PARTIALLY OVERLAPPING WITH A STEROID-RECEPTOR BINDING-SITE [J].
ALTSCHMIED, J ;
MULLER, M ;
BANIAHMAD, A ;
STEINER, C ;
RENKAWITZ, R .
NUCLEIC ACIDS RESEARCH, 1989, 17 (13) :4975-4991
[2]  
Ausubel FM, 1987, CURRENT PROTOCOLS MO
[3]   MODULAR STRUCTURE OF A CHICKEN LYSOZYME SILENCER - INVOLVEMENT OF AN UNUSUAL THYROID-HORMONE RECEPTOR-BINDING SITE [J].
BANIAHMAD, A ;
STEINER, C ;
KOHNE, AC ;
RENKAWITZ, R .
CELL, 1990, 61 (03) :505-514
[4]   CHROMATIN STRUCTURE IS REQUIRED TO BLOCK TRANSCRIPTION OF THE METHYLATED HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE [J].
BUSCHHAUSEN, G ;
WITTIG, B ;
GRAESSMANN, M ;
GRAESSMANN, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (05) :1177-1181
[5]   DNA METHYLATION AND GENE ACTIVITY [J].
CEDAR, H .
CELL, 1988, 53 (01) :3-4
[6]   DEVELOPMENTAL REGULATION OF BETA-GLOBIN GENE SWITCHING [J].
CHOI, ORB ;
ENGEL, JD .
CELL, 1988, 55 (01) :17-26
[7]   MOUSE LYSOZYME-M GENE - ISOLATION, CHARACTERIZATION, AND EXPRESSION STUDIES [J].
CROSS, M ;
MANGELSDORF, I ;
WEDEL, A ;
RENKAWITZ, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (17) :6232-6236
[8]   REPETITIVE SEQUENCE INVOLVEMENT IN THE DUPLICATION AND DIVERGENCE OF MOUSE LYSOZYME GENES [J].
CROSS, M ;
RENKAWITZ, R .
EMBO JOURNAL, 1990, 9 (04) :1283-1288
[9]   DNA METHYLATION AND GENE ACTIVITY [J].
DOERFLER, W .
ANNUAL REVIEW OF BIOCHEMISTRY, 1983, 52 :93-124
[10]  
DOERFLER W, 1990, NUCL ACID METHYLATIO, P329