Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1
Program in Gene Function and Expression
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.
DOI of Published Version
Mol Cell. 2005 Feb 4;17(3):453-62. Link to article on publisher's site
Vakoc CR, Letting DL, Gheldof N, Sawado T, Bender MA, Groudine M, Weiss MJ, Dekker J, Blobel GA. (2005). Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1. Program in Gene Function and Expression Publications. https://doi.org/10.1016/j.molcel.2004.12.028. Retrieved from https://escholarship.umassmed.edu/pgfe_pp/132