Abstract
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.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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CCCTC-Binding Factor
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Cell Nucleus / metabolism
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Chickens
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Conserved Sequence
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism*
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Deoxyribonuclease I
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Enhancer Elements, Genetic*
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Genetic Variation
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Globins / genetics
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Humans
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K562 Cells
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Molecular Sequence Data
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Oligodeoxyribonucleotides / chemistry
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Oligodeoxyribonucleotides / metabolism
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Protein Biosynthesis
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Repressor Proteins*
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Transcription Factors / chemistry
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
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Vertebrates
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Zinc Fingers
Substances
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CCCTC-Binding Factor
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CTCF protein, human
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DNA-Binding Proteins
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Oligodeoxyribonucleotides
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Repressor Proteins
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Transcription Factors
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Globins
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Deoxyribonuclease I