Many transcription factors contain proline- or glutamine-rich activati
on domains. Here it is shown that simple homopolymeric stretches of th
ese amino acids can activate transcription when fused to the DNA bindi
ng domain of GAL4 factor. In vitro, activity increased with polymer le
ngth, whereas in cell transfection assays maximal activity was achieve
d by 10 to 30 glutamines or about 10 prolines. Similar results were ob
tained when glutamine stretches were placed within a [GAL4]-VP16 chime
ric protein. Because these stretches are encoded by rapidly evolving t
riplet repeats (microsatellites), they may be the main cause for modul
ation of transcription factor activity and thus result ir subtle or ov
ert genomic effects.