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Mol Cell Biol, May 1998, p. 2444-2454, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Intrinsic Transcriptional Activation-Inhibition Domains of the Polyomavirus Enhancer Binding Protein 2/Core Binding Factor  Subunit Revealed in the Presence of the  Subunit

Tomohiko Kanno, Yuka Kanno, Lin-Feng Chen, Eiko Ogawa, Woo-Young Kim, and Yoshiaki Ito^*

Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606, Japan

Received 17 December 1997/Returned for modification 30 January 1998/Accepted 9 February 1998

A member of the polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF) is composed of PEBP2B1/AML1 (as the  subunit) and a  subunit. It plays an essential role in definitive hematopoiesis and is frequently involved in the chromosomal abnormalities associated with leukemia. In the present study, we report functionally separable modular structures in PEBP2B1 for DNA binding and for transcriptional activation. DNA binding through the Runt domain of PEBP2B1 was hindered by the adjacent carboxy-terminal region, and this inhibition was relieved by interaction with the  subunit. Utilizing a reporter assay system in which both the  and  subunits are required to achieve strong transactivation, we uncovered the presence of transcriptional activation and inhibitory domains in PEBP2B1 that were only apparent in the presence of the  subunit. The inhibitory domain keeps the full transactivation potential of full-length PEBP2B1 below its maximum potential. Fusion of the transactivation domain of PEBP2B1 to the yeast GAL4 DNA-binding domain conferred transactivation potential, but further addition of the inhibitory domain diminished the activity. These results suggest that the activity of the  subunit as a transcriptional activator is regulated intramolecularly as well as by the  subunit. PEBP2B1 and the  subunit were targeted to the nuclear matrix via signals distinct from the nuclear localization signal. Moreover, the transactivation domain by itself was capable of associating with the nuclear matrix, which implies the existence of a relationship between transactivation and nuclear matrix attachment.

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^* Corresponding author. Mailing address: Institute for Virus Research, Kyoto University, Shogo-in, Sakyo-ku, Kyoto 606, Japan. Phone: 81-75-751-4028. Fax: 81-75-752-3232. E-mail: yito{at}virus.kyoto-u.ac.jp.

Present address: Department of Genetics and Pediatrics, The Children's Hospital, Boston, MA 02115.

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Mol Cell Biol, May 1998, p. 2444-2454, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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