Context-dependent EKLF responsiveness defines the developmental specificity of the human epsilon-globin gene in erythroid cells of YAC transgenic mice

Article Abstract:

Context-dependent erythroid kruppel-like factor (EKLF) responsiveness has been found to define developmental specificity of the human epsilon-globin gene in erythroid cells of YAC transgenic mice. A study focused on the globin CAAT and CAC promoter motifs has been carried out with a high-affinity CAC-binding site for the EKLF placed in the epsilon-globin promoter repeat element. Suppression of epsilon globin transcription in definitive erythropoiesis is mediated by the binding of a repressor that prevents EKLF from activating the epsilon-globin gene.

United States, Netherlands, Usage, Embryology, Experimental, Embryological research, Genetically modified mice

The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription

Article Abstract:

TR2/TR4 directly represses Gata1/GATA1 transcription in murine and human erythroid progenitor cells through an evolutionarily conserved binding site thereby providing a mechanism by which Gata1 can be directly silenced during terminal erythroid maturation.

Science & research, Messenger RNA, DNA-ligand interactions, DNA binding

Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the beta-globin locus control region in vivo

Article Abstract:

In the beta-globin cluster the locus-control region has five DNase I hypersensitive sites (5'HS1-5) necessary for locus activation, and 5'HS3 includes six G-rich motifs necessary for its activity. Members of a protein family that are characterized by zinc fingers very homologous to those of transcription factor Sp1 interact with the motifs. The function of such closely related proteins can be distinguished in vivo through the matching of point mutations in 5'HS3 to amino acid changes in the zinc fingers of EKLF and Sp1. Testing in transgenic mice confirms that EKLF directly activates 5'HS3.

Observations, Binding sites (Biochemistry), Active sites (Biochemistry), DNA binding proteins