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ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation


Transcription factors carry functional domains, which are often physically distinct, for sequence-specific DNA binding, transcriptional activation and regulatory functions. The transcription factor ATF-2 is a DNA-binding protein that binds to cyclic AMP-response elements (CREs), forms a homodimer or heterodimer with c-Jun, and stimulates CRE-dependent transcription1,2,3. Here we report that ATF-2 is a histone acetyltransferase (HAT), which specifically acetylates histones H2B and H4 in vitro. Motif A, which is located in the HAT domain, is responsible for the stimulation of CRE-dependent transcription; moreover, in response to ultraviolet irradiation, phosphorylation of ATF-2 is accompanied by enhanced HAT activity of ATF-2 and CRE-dependent transcription. These results indicate that phosphorylation of ATF-2 controls its intrinsic HAT activity and its action on CRE-dependent transcription. ATF-2 may represent a new class of sequence-specific factors, which are able to activate transcription by direct effects on chromatin components.

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Figure 1: HAT activities of p300 and ATF-2.
Figure 2: ATF-2 selectively acetylated human histones H2B and H4 in vitro.
Figure 3: The proline-rich domain of ATF-2 has intrinsic HAT activity.
Figure 4: Phosphorylation of ATF-2 enhances its intrinsic HAT activity and CRE-dependent transcription.

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We thank T. Nakajima, S. Ishii, N. Jones, M. Green and M. Karin for providing reagents; C. Geltinger, G. Gachelin, T-P. Yao, D. M. Livingston, A. P. Wolffe and R. Eckner for discussions; and N. Day, A. Körner and B. C. An der Lan for critical reading of the manuscript. This work was supported by the NIH (R.C., Y.N., K.I.), by the Special Cooperation Funds of the Science and Technology Agency, and by Grants-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan (K.K.Y.).

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Correspondence to Kazunari K. Yokoyama.

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Kawasaki, H., Schiltz, L., Chiu, R. et al. ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation. Nature 405, 195–200 (2000).

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