Interaction of ETS-1 and ERGB/FLI-1 proteins with DNA is modulated by spacing between multiple binding sites as well as phosphorylation

ETS is a family of transcription factors that contain a highly conserved ETS DNA binding domain. Various members of the ETS family are expressed in cells of hematopoietic lineage. ETS-1, ETS-2 and ERGB/FLI-1 are expressed at high levels in T-lymphocytes. HIV-1 infects T-cells and it has been shown that its LTR contains binding sites for various transcription factors. In this study we show that the HIV-1 core enhancer is directly regulated by ERGB/FLI-1 protein positively, as well as, negatively, depending upon the presence or absence of accessory factors in different cell types. In addition, we show that the ETS-1 transactivation activity is enhanced upon dephosphorylation of the Calmodulin-dependant Protein Kinase II phosphorylation site located in exon VII. Finally, we demonstrate that the spacing two EBS cores in palindromic or direct play a crucial role in binding of ETS proteins to DNA.