The protein CTCF is required for the enhancer blocking activity of vertebrate insulators

被引:877
作者
Bell, AC [1 ]
West, AG [1 ]
Felsenfeld, G [1 ]
机构
[1] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1016/S0092-8674(00)81967-4
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
An insulator is a DNA sequence that can act as a barrier to the influences of neighboring cis-acting elements, preventing gene activation, for example, when located between an enhancer and a promoter. We have identified a 42 bp fragment of the chicken beta-globin insulator that is both necessary and sufficient for enhancer blocking activity in human cells. We show that this sequence is the binding site for CTCF, a previously identified eleven-zinc finger DNA-binding protein that is highly conserved in vertebrates. CTCF sites are present in all of the vertebrate enhancer-blocking elements we have examined. We suggest that directional enhancer blocking by CTCF is a conserved component of gene regulation in vertebrates.
引用
收藏
页码:387 / 396
页数:10
相关论文
共 38 条
[21]   A POSITION-EFFECT ASSAY FOR BOUNDARIES OF HIGHER-ORDER CHROMOSOMAL DOMAINS [J].
KELLUM, R ;
SCHEDL, P .
CELL, 1991, 64 (05) :941-950
[22]   A GROUP OF SCS ELEMENTS FUNCTION AS DOMAIN BOUNDARIES IN AN ENHANCER-BLOCKING ASSAY [J].
KELLUM, R ;
SCHEDL, P .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (05) :2424-2431
[23]   Molecular weight abnormalities of the CTCF transcription factor: CTCF migrates aberrantly in SDS-PAGE and the size of the expressed protein is affected by the UTRs and sequences within the coding region of the CTCF gene [J].
Klenova, EM ;
Nicolas, RH ;
U, S ;
Carne, AF ;
Lee, RE ;
Lobanenkov, VV ;
Goodwin, GH .
NUCLEIC ACIDS RESEARCH, 1997, 25 (03) :466-473
[24]   CTCF, A CONSERVED NUCLEAR FACTOR REQUIRED FOR OPTIMAL TRANSCRIPTIONAL ACTIVITY OF THE CHICKEN C-MYC GENE, IS AN 11-ZN-FINGER PROTEIN DIFFERENTIALLY EXPRESSED IN MULTIPLE FORMS [J].
KLENOVA, EM ;
NICOLAS, RH ;
PATERSON, HF ;
CARNE, AF ;
HEATH, CM ;
GOODWIN, GH ;
NEIMAN, PE ;
LOBANENKOV, VV .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (12) :7612-7624
[25]   DNA-SEQUENCES FOR TYPICAL RIBOSOMAL GENE SPACERS FROM XENOPUS-LAEVIS AND XENOPUS-BOREALIS [J].
LABHART, P ;
REEDER, RH .
NUCLEIC ACIDS RESEARCH, 1987, 15 (08) :3623-3624
[26]  
LOBANENKOV VV, 1990, ONCOGENE, V5, P1743
[27]   GAGA mediates the enhancer blocking activity of the eve promoter in the Drosophila embryo [J].
Ohtsuki, S ;
Levine, M .
GENES & DEVELOPMENT, 1998, 12 (21) :3325-3330
[28]   Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators [J].
Pikaart, MI ;
Recillas-Targa, F ;
Felsenfeld, G .
GENES & DEVELOPMENT, 1998, 12 (18) :2852-2862
[29]   An insulator element and condensed chromatin region separate the chicken β-globin locus from an independently regulated erythroid-specific folate receptor gene [J].
Prioleau, MN ;
Nony, P ;
Simpson, M ;
Felsenfeld, G .
EMBO JOURNAL, 1999, 18 (14) :4035-4048
[30]   DEVELOPMENTAL REGULATION OF TOPOISOMERASE-II SITES AND DNASE I-HYPERSENSITIVE SITES IN THE CHICKEN-BETA-GLOBIN LOCUS [J].
REITMAN, M ;
FELSENFELD, G .
MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (06) :2774-2786