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Molecular and Cellular Biology, March 2000, p. 2031-2042, Vol. 20, No. 6
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

p300 Requires Its Histone Acetyltransferase Activity and SRC-1 Interaction Domain To Facilitate Thyroid Hormone Receptor Activation in Chromatin

Jiwen Li, Bert W. O'Malley, and Jiemin Wong*

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030

Received 22 October 1999/Returned for modification 4 December 1999/Accepted 14 December 1999

We have characterized the mechanism by which coactivator p300 facilitates transcriptional activation mediated by the heterodimer of thyroid hormone (T3) receptor and 9-cis retinoid acid receptor (TR-RXR) in the context of chromatin. We demonstrate that, while p300 can enhance the transcriptional activation mediated by both liganded TR-RXR and GAL4-VP16, its histone acetyltransferase activity (HAT) is required for its ability to facilitate liganded TR-RXR- but not GAL4-VP16-mediated transcriptional activation. To understand how p300 is recruited by liganded TR-RXR, we have analyzed the interactions between TR-RXR and p300 as well as SRC-1 family coactivators. We show that, in contrast to a strong hormone-dependent interaction between TR-RXR and SRC-1 family coactivators, p300 displays minimal, if any, T3-dependent interaction with TR-RXR. However, p300 can be recruited by liganded TR-RXR through its interaction with SRC-1 family coactivators. Consistent with the protein-protein interaction profile described above, we demonstrate that the SRC-1 interaction domain of p300 is important for its ability to facilitate transcriptional activation mediated by TR-RXR, whereas its nuclear receptor interaction domain is dispensable. Collectively, these results reveal the functional significance of the HAT activity of p300 and define an indirect mode for the action of p300 in TR-RXR activation.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6291. Fax: (713) 790-1275. E-mail: jwong{at}bcm.tmc.edu.

Molecular and Cellular Biology, March 2000, p. 2031-2042, Vol. 20, No. 6
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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