Eukaryotic gene transcription is regulated by sequence-specific transcription factors that bind modular cis acting promoter 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-1 is shown to play a key role in the induction of NOX1, this protein binds the cAMP response element (CRE) and mediates PKA-induced stimulation of CRE-reporter genes. ATF-2 forms homodimers and heterodimers with c-Jun to initiate CREdependent 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 functions as a histone acetyltransferase (HAT) and acetylates Histones H2B and H4 specifically in vitro.
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