Abstract
Recent evidence suggests that long-range enhancers and gene promoters are in close proximity, which might reflect the formation of chromatin loops. Here, we examined the mechanism for DNA looping at the beta-globin locus. By using chromosome conformation capture (3C), we show that the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 are required for the physical interaction between the beta-globin locus control region (LCR) and the beta-major globin promoter. Kinetic studies reveal that GATA-1-induced loop formation correlates with the onset of beta-globin transcription and occurs independently of new protein synthesis. GATA-1 occupies the beta-major globin promoter normally in fetal liver erythroblasts from mice lacking the LCR, suggesting that GATA-1 binding to the promoter and LCR are independent events that occur prior to loop formation. Together, these data demonstrate that GATA-1 and FOG-1 are essential anchors for a tissue-specific chromatin loop, providing general insights into long-range enhancer function.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Binding Sites / genetics
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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DNA / chemistry
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DNA / genetics
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DNA / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Enhancer Elements, Genetic
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Erythroid-Specific DNA-Binding Factors
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GATA1 Transcription Factor
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Genes, Regulator*
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Globins / genetics*
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Humans
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Locus Control Region
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Mice
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Mice, Mutant Strains
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Nucleic Acid Conformation
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Promoter Regions, Genetic
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Protein Binding
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RNA Polymerase II / genetics
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RNA Polymerase II / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Erythroid-Specific DNA-Binding Factors
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GATA1 Transcription Factor
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GATA1 protein, human
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Gata1 protein, mouse
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Nuclear Proteins
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Transcription Factors
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ZFPM1 protein, human
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Zfpm1 protein, mouse
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Globins
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DNA
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RNA Polymerase II