An activation function in Pit-1 required selectively for synergistic transcription.
Synergistic transcription activation is a key component in the generation of the spectrum of eukaryotic promoter activities by a limited number of transcription factors. Various mechanisms could account for synergy, but a central question remains of whether synergism requires transcription factor functions that differ from those that direct independent activation. The rat growth hormone promoter is synergistically activated by the pituitary-specific transcription factor, Pit-1, and the thyroid hormone receptor (TR). Mutations that disrupted the previously described DNA binding and transcriptional activation domains of both Pit-1 and TR reduced Pit-1/TR synergy in parallel with their effects on the much weaker, independent Pit-1 and TR activations of the rat growth hormone promoter. Thus, Pit-1 and TR amplify each other's intrinsic activities. Mutations of Pit-1 that selectively inhibited synergism with the TR without affecting independent Pit-1 activity were also identified. Pit-1/TR synergy is therefore a consequence of a novel synergism-selective activity and synergism-independent Pit-1 and TR functions.
Chang
W
W
Metabolic Research Unit, University of California, San Francisco, California 94143-0540, USA.
Zhou
W
W
Theill
L E
LE
Baxter
J D
JD
Schaufele
F
F
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004357:Drug Synergism; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C494186:Pou1f1 protein, rat; D011988:Receptors, Thyroid Hormone; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D004247:DNA