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Publication : ATF2 is required for amino acid-regulated transcription by orchestrating specific histone acetylation.

First Author  Bruhat A Year  2007
Journal  Nucleic Acids Res Volume  35
Issue  4 Pages  1312-21
PubMed ID  17267404 Mgi Jnum  J:121664
Mgi Id  MGI:3710913 Doi  10.1093/nar/gkm038
Citation  Bruhat A, et al. (2007) ATF2 is required for amino acid-regulated transcription by orchestrating specific histone acetylation. Nucleic Acids Res 35(4):1312-21
abstractText  The transcriptional activation of CHOP (a CCAAT/enhancer-binding protein-related gene) by amino acid deprivation involves the activating transcription factor 2 (ATF2) and the activating transcription factor 4 (ATF4) binding the amino acid response element (AARE) within the promoter. Using a chromatin immunoprecipitation approach, we report that in vivo binding of phospho-ATF2 and ATF4 to CHOP AARE are associated with acetylation of histones H4 and H2B in response to amino acid starvation. A time course analysis reveals that ATF2 phosphorylation precedes histone acetylation, ATF4 binding and the increase in CHOP mRNA. We also show that ATF4 binding and histone acetylation are two independent events that are required for the CHOP induction upon amino acid starvation. Using ATF2-deficient mouse embryonic fibroblasts, we demonstrate that ATF2 is essential in the acetylation of histone H4 and H2B in vivo. The role of ATF2 on histone H4 acetylation is dependent on its binding to the AARE and can be extended to other amino acid regulated genes. Thus, ATF2 is involved in promoting the modification of the chromatin structure to enhance the transcription of a number of amino acid-regulated genes.
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