Eukaryotic gene transcription is regulated by sequence-specific transcription factors which bind modular cis-acting promotor and enhancer elements. The ATF/CREB transcription factor family binds the palindromic cAMP response element (CRE) octanucleotide TGACGTCA. The ATF/CREB family includes CREB-1, CREB-2 (also designated ATF-4), ATF-1, ATF-2 and ATF-3. This family of proteins contain highly divergent N-terminal domains, but share a C-terminal leucine zipper for dimerization and DNA binding. ATF-2 forms homodimers and heterodimers with c-Jun to initiate CRE-dependent transcription. Phosphorylation of ATF-2 at Thr 69 and Thr 71 by stress-activated kinases is necessary for transcriptional activation. Myc also induces phosphorylation of ATF-2 at Thr 69 and Thr 71 to prolong the half-life of ATF-2. ATF-2 also functions as a histone acetyltransferase (HAT) by specifically acetylating histones H2B and H4 in vitro. The gene encoding human ATF-2 maps to chromosome 2q31.1.
