DNA binding of USF is required for specific E-box dependent gene activation in vivo.
Although USF-1 and -2 are the major proteins that bind to Myc-regulated E-box (CACGTG) elements in many cells, there is no clear role for USF during Myc-dependent gene regulation. Using dominant negative alleles of USF-1 we now show that DNA binding by USF at a Myc-regulated E-box limits the ability of another E-box binding factor, TFE-3, to activate a target gene of Myc in vivo and to stimulate S phase entry in resting fibroblasts. Similarly, dominant negative alleles of USF-1 relieve the restriction that prevents activation of the IgH enhancer by TFE-3 in non B-cells. DNA binding activity of USF complexes is abundant in primary human B-cells and is significantly downregulated during B-cell immortalization. Re-expression of USF-1 in immortalized B-cells retards proliferation. Our data establish an essential role for USF in restricting E-box dependent gene activation in vivo and suggest that this control is relaxed during cellular immortalization.
Kiermaier
A
A
Institute for Molecular Biology and Tumour Research, University of Marburg, Emil-Mannkopff-Str 2, 35033 Marburg, Germany.
Gawn
J M
JM
Desbarats
L
L
Saffrich
R
R
Ansorge
W
W
Farrell
P J
PJ
Eilers
M
M
Packham
G
G
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D016259:Genes, myc; D006367:HeLa Cells; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D016350:Leucine Zippers; D051379:Mice; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D004247:DNA