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 prot ein that binds to cyclic AMP-response elements (CREs), forms a homodimer or heterodimer with c-Jun, and stimulates CRE-dependent transcription(1-3). H ere we report that ATF-2 is a histone acetyltransferase (HAT), which specif ically acetylates histones H2B and H4 in vitro. Motif A, which is located i n the HAT domain, is responsible for the stimulation of CRE-dependent trans cription; moreover, in response to ultraviolet irradiation, phosphorylation of ATF-2 is accompanied by enhanced HAT activity of ATF-2 and CRE-dependen t transcription. These results indicate that phosphorylation of ATF-2 contr ols its intrinsic HAT activity and its action on CRE-dependent transcriptio n. ATF-2 may represent a new class of sequence-specific factors, which are able to activate transcription by direct effects on chromatin components.