title: K-Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation.
abstract: Neuronal histone acetylation has been linked to memory consolidation, and targeting histone acetylation has emerged as a promising therapeutic strategy for neuropsychiatric diseases. However, the role of histone-modifying enzymes in the adult brain is still far from being understood. Here we use RNA sequencing to screen the levels of all known histone acetyltransferases (HATs) in the hippocampal CA1 region and find that K-acetyltransferase 2a (Kat2a)--a HAT that has not been studied for its role in memory function so far--shows highest expression. Mice that lack Kat2a show impaired hippocampal synaptic plasticity and long-term memory consolidation. We furthermore show that Kat2a regulates a highly interconnected hippocampal gene expression network linked to neuroactive receptor signaling via a mechanism that involves nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In conclusion, our data establish Kat2a as a novel and essential regulator of hippocampal memory consolidation.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany.
authors.forename: Roman M
authors.initials: RM
authors.lastname: Stilling
authors.affiliation: Research group for Pathophysiology in Dementia, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
authors.forename: Raik
authors.initials: R
authors.lastname: Rönicke
authors.affiliation: Research group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Benito
authors.affiliation: Research group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Urbanke
authors.affiliation: Research group for Computational Analysis of Biological Networks, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Capece
authors.affiliation: Research group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Burkhardt
authors.affiliation: Research group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Bahari-Javan
authors.affiliation: Research group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Barth
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany.
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Sananbenesi
authors.affiliation: Research group for Computational Analysis of Biological Networks, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Schütz
authors.affiliation: Research group for Computational Analysis of Biological Networks, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Dyczkowski
authors.affiliation: Research group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Martinez-Hernandez
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany.
authors.forename: Cemil
authors.initials: C
authors.lastname: Kerimoglu
authors.affiliation: MD Anderson Cancer Center, University of Texas, Smithville, TX, USA.
authors.forename: Sharon Y R
authors.initials: SY
authors.lastname: Dent
authors.affiliation: Research group for Computational Analysis of Biological Networks, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bonn
authors.affiliation: Research group for Pathophysiology in Dementia, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Reymann
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany Research group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany afische2@gwdg.de.
authors.forename: Andre
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000201:enzymology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D000099224:p300-CBP-Associated Factor
chemical_list: D051548:Histone Acetyltransferases; C501178:Gcn5l2 protein, mouse; D000099224:p300-CBP-Associated Factor
keywords: epigenetics; histone acetylation; histone acetyltransferases; learning; memory