title: The bZIP repressor proteins, c-Jun dimerization protein 2 and activating transcription factor 3, recruit multiple HDAC members to the ATF3 promoter.
abstract: JDP2, is a basic leucine zipper (bZIP) protein displaying a high degree of homology with the stress inducible transcription factor, ATF3. Both proteins bind to cAMP and TPA response elements and repress transcription by multiple mechanisms. Histone deacetylases (HDACs) play a key role in gene inactivation by deacetylating lysine residues on histones. Here we describe the association of JDP2 and ATF3 with HDACs 1, 2-6 and 10. Association of HDAC3 and HDAC6 with JDP2 and ATF3 occurs via direct protein-protein interactions. Only part of the N-terminal bZIP motif of JDP2 and ATF3 basic domain is necessary and sufficient for the interaction with HDACs in a manner that is independent of coiled-coil dimerization. Class I HDACs associate with the bZIP repressors via the DAC conserved domain whereas the Class IIb HDAC6 associates through its C-terminal unique binder of ubiquitin Zn finger domain. Both JDP2 and ATF3 are known to bind and repress the ATF3 promoter. MEF cells treated with histone deacetylase inhibitor, trichostatin A (TSA) display enhanced ATF3 transcription. ATF3 enhanced transcription is significantly reduced in MEF cells lacking both ATF3 and JDP2. Collectively, we propose that the recruitment of multiple HDAC members to JDP2 and ATF3 is part of their transcription repression mechanism.
authors.affiliation: Department of Molecular Genetics, Technion-Israel Institute of Technology, Haifa, Israel. ilona.darlyuk@gmail.com
authors.forename: Ilona
authors.initials: I
authors.lastname: Darlyuk-Saadon
authors.forename: Keren
authors.initials: K
authors.lastname: Weidenfeld-Baranboim
authors.forename: Kazunari K
authors.initials: KK
authors.lastname: Yokoyama
authors.forename: Tsonwin
authors.initials: T
authors.lastname: Hai
authors.forename: Ami
authors.initials: A
authors.lastname: Aronheim
mesh_terms: D051700:Activating Transcription Factor 3 / Q000096:biosynthesis* / Q000235:genetics; D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000502:physiology*; D055503:Protein Multimerization / Q000187:drug effects / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D016335:Zinc Fingers
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C491387:JDP2 protein, human; C491386:Jundp2 protein, mouse; D012097:Repressor Proteins; C012589:trichostatin A; D006655:Histone Deacetylases