title: Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation.
abstract: Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of long-term memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied garcinol, an inhibitor of the HATs of the p300 (EP300 binding protein)/CBP (CREB-binding protein) family, and the HATs of the PCAF (p300/CBP-associated factor) family. As comparative agent we applied C646, a specific inhibitor that selectively blocks HATS of the p300/CBP family. Immunochemical analysis reveals differences in histone H3 acetylation in the honeybee brain, in response to the injection of either C646 or garcinol. Behavioral assessment reveals that the two drugs cause memory impairment of different nature when injected after associative conditioning: processes disturbed by garcinol are annihilated by the established transcription blocker actinomycin D and thus seem to require transcription processes. Actions of C646 are unaltered by actinomycin D, and thus seem to be independent of transcription. The outcome of our different approaches as summarized suggests that distinct HATs contribute to different acetylation-mediated processes in memory formation. We further deduce that the acetylation-mediated processes in memory formation comprise transcription-dependent and transcription-independent mechanisms.
authors.affiliation: Department 8.3 Biosciences Zoology/Physiology-Neurobiology, ZHMB (Center of Human and Molecular Biology), Faculty 8 - Natural Science and Technology III, Saarland University, D-66041 Saarbrücken, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Merschbaecher
authors.affiliation: Department 8.3 Biosciences Zoology/Physiology-Neurobiology, ZHMB (Center of Human and Molecular Biology), Faculty 8 - Natural Science and Technology III, Saarland University, D-66041 Saarbrücken, Germany.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Hatko
authors.affiliation: Department 8.3 Biosciences Zoology/Physiology-Neurobiology, ZHMB (Center of Human and Molecular Biology), Faculty 8 - Natural Science and Technology III, Saarland University, D-66041 Saarbrücken, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Folz
authors.affiliation: Department 8.3 Biosciences Zoology/Physiology-Neurobiology, ZHMB (Center of Human and Molecular Biology), Faculty 8 - Natural Science and Technology III, Saarland University, D-66041 Saarbrücken, Germany uli.mueller@mx.uni-saarland.de.
authors.forename: Uli
authors.initials: U
authors.lastname: Mueller
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects / Q000502:physiology; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D001516:Bees; D001565:Benzoates / Q000008:administration & dosage; D001921:Brain / Q000201:enzymology*; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009578:Nitrobenzenes; D011720:Pyrazoles / Q000008:administration & dosage; D047069:Pyrazolones; D013729:Terpenes / Q000008:administration & dosage; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors
chemical_list: C584509:4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid; D001565:Benzoates; D006657:Histones; D009578:Nitrobenzenes; D011720:Pyrazoles; D047069:Pyrazolones; D013729:Terpenes; D051548:Histone Acetyltransferases; D050880:p300-CBP Transcription Factors; C054597:garcinol