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-dependent Protein Kinase II phosphorylation site located in exon VII. Finally, we demonstrate that the spacing between the two EBS cores in palindromic or direct repeat sites play a crucial role in binding of ETS proteins to DNA.
Hodge
D R
DR
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, MD 21702-1201, USA.
Robinson
L
L
Watson
D
D
Lautenberger
J
J
Zhang
X K
XK
Venanzoni
M
M
Seth
A
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D016325:HIV Long Terminal Repeat; D008969:Molecular Sequence Data; D010766:Phosphorylation; D050784:Proto-Oncogene Protein c-ets-1; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D018411:Spodoptera; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050784:Proto-Oncogene Protein c-ets-1; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA