Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1
Program in Gene Function and Expression
Medical Subject Headings
Animals; Base Sequence; Binding Sites; Carrier Proteins; Cell Line; DNA; DNA-Binding Proteins; Enhancer Elements, Genetic; Erythroid-Specific DNA-Binding Factors; GATA1 Transcription Factor; *Genes, Regulator; Globins; Humans; Locus Control Region; Mice; Mice, Mutant Strains; Nuclear Proteins; Nucleic Acid Conformation; Promoter Regions, Genetic; Protein Binding; RNA Polymerase II; Transcription Factors
Genetics and Genomics
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.
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Citation: Mol Cell. 2005 Feb 4;17(3):453-62. Link to article on publisher's site