Chameau HAT and DRpd3 HDAC function as antagonistic cofactors of JNK/AP-1-dependent transcription during Drosophila metamorphosis.
Gene regulation by AP-1 transcription factors in response to Jun N-terminal kinase (JNK) signaling controls essential cellular processes during development and in pathological situations. Here, we report genetic and molecular evidence that the histone acetyltransferase (HAT) Chameau and the histone deacetylase DRpd3 act as antagonistic cofactors of DJun and DFos to modulate JNK-dependent transcription during thorax metamorphosis and JNK-induced apoptosis in Drosophila. We demonstrate in cultured cells that DFos phosphorylation mediated by JNK signaling plays a central role in coordinating the dynamics of Chameau and DRpd3 recruitment and function at AP-1-responsive promoters. Activating the pathway stimulates the HAT function of Chameau, promoting histone H4 acetylation and target gene transcription. Conversely, in response to JNK signaling inactivation, DRpd3 is recruited and suppresses histone acetylation and transcription. This study establishes a direct link among JNK signaling, DFos phosphorylation, chromatin modification, and AP-1-dependent transcription and its importance in a developing organism.
Miotto
Benoit
B
Laboratoire de Génétique et Physiologie du Développement, Institut de Biologie du Développement de Marseille, CNRS/INSERM/Université de la Méditerranée, Parc Scientifique de Luminy, 13288 Marseille Cedex 9, France.
Sagnier
Thierry
T
Berenger
Hélène
H
Bohmann
Dirk
D
Pradel
Jacques
J
Graba
Yacine
Y
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000502:physiology*; D008675:Metamorphosis, Biological; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D006657:Histones; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C435749:kay protein, Drosophila; D000123:Acetyltransferases; C467710:chm protein, Drosophila; D048670:MAP Kinase Kinase 4; C512966:HDAC1 protein, Drosophila; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases