Proximity among Distant Regulatory Elements at the β-Globin Locus Requires GATA-1 and FOG-1

Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Molecular Cell (Impact Factor: 14.46). 03/2005; 17(3):453-62. DOI: 10.1016/j.molcel.2004.12.028
Source: PubMed

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.

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