The p300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid-regulated transcription of CHOP.
When an essential amino acid is limited, a signaling cascade is triggered that leads to increased translation of the 'master regulator', activating transcription factor 4 (ATF4), and resulting in the induction of specific target genes. Binding of ATF4 to the amino acid response element (AARE) is an essential step in the transcriptional activation of CHOP (a CCAAT/enhancer-binding protein-related gene) by amino acid deprivation. We set out to identify proteins that interact with ATF4 and that play a role in the transcriptional activation of CHOP. Using a tandem affinity purification (TAP) tag approach, we identified p300/CBP-associated factor (PCAF) as a novel interaction partner of ATF4 in leucine-starved cells. We show that the N-terminal region of ATF4 is required for a direct interaction with PCAF and demonstrate that PCAF is involved in the full transcriptional response of CHOP by amino acid starvation. Chromatin immunoprecipitation analysis revealed that PCAF is engaged on the CHOP AARE in response to amino acid starvation and that ATF4 is essential for its recruitment. We also show that PCAF stimulates ATF4-driven transcription via its histone acetyltransferase domain. Thus PCAF acts as a coactivator of ATF4 and is involved in the enhancement of CHOP transcription following amino acid starvation.
Chérasse
Yoan
Y
UMR 1019 of Human Nutrition and Proteomic core facility, INRA de Theix, 63122 Saint Genès Champanelle, France.
Maurin
Anne-Catherine
AC
Chaveroux
Cédric
C
Jousse
Céline
C
Carraro
Valérie
V
Parry
Laurent
L
Deval
Christiane
C
Chambon
Christophe
C
Fafournoux
Pierre
P
Bruhat
Alain
A
D051701:Activating Transcription Factor 4 / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000502:physiology; D051379:Mice; D017434:Protein Structure, Tertiary; D020218:Response Elements; D051742:Transcription Factor CHOP / Q000235:genetics*; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D051701:Activating Transcription Factor 4; D000596:Amino Acids; D007930:Leucine; D051742:Transcription Factor CHOP; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C497109:ATF4 protein, human