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Volume 271, Number 30, Issue of July 26, 1996 pp. 17733-17738
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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An Activation Function in Pit-1 Required Selectively for Synergistic Transcription

(Received for publication, March 5, 1996, and in revised form, May 9, 1996)

Winston Chang , Wen Zhou , Lars E. Theill , John D. Baxter and Fred Schaufele

From the Metabolic Research Unit, University of California, San Francisco, California 94143-0540 and  Amgen, Thousand Oaks, California 91320

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.

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