Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1

Mol Cell. 2005 Feb 4;17(3):453-62. doi: 10.1016/j.molcel.2004.12.028.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Genes, Regulator*
  • Globins / genetics*
  • Humans
  • Locus Control Region
  • Mice
  • Mice, Mutant Strains
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleic Acid Conformation
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Gata1 protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • ZFPM1 protein, human
  • Zfpm1 protein, mouse
  • Globins
  • DNA
  • RNA Polymerase II