ATF2 is required for amino acid-regulated transcription by orchestrating specific histone acetylation.
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.
Bruhat
Alain
A
UMR 1019, Unité de Nutrition Humaine, INRA de Theix, 63122 Saint Genès Champanelle, France. bruhat@clermont.inra.fr
Chérasse
Yoan
Y
Maurin
Anne-Catherine
AC
Breitwieser
Wolfgang
W
Parry
Laurent
L
Deval
Christiane
C
Jones
Nic
N
Jousse
Céline
C
Fafournoux
Pierre
P
D000107:Acetylation; D051698:Activating Transcription Factor 2 / Q000502:physiology*; D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006657:Histones / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D020218:Response Elements; D051742:Transcription Factor CHOP / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation
D051698:Activating Transcription Factor 2; D000596:Amino Acids; C497106:Atf2 protein, mouse; C081452:Atf4 protein, mouse; D006657:Histones; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP