Histone Acetylation Determines Transcription of Atypical Protein Kinases in Rat Neurons

Overview

Journal Sci Rep

Specialty Science

Date 2019 Mar 15

PMID 30867503

Citations 5

Authors

Anastasia A Borodinova

Maria A Kuznetsova

Victoria S Alekseeva

Pavel M Balaban

Affiliations

Soon will be listed here.

Abstract

It is widely accepted that memory consolidation requires de-novo transcription of memory-related genes. Epigenetic modifications, particularly histone acetylation, may facilitate gene transcription, but their potential molecular targets are poorly characterized. In the current study, we addressed the question of epigenetic control of atypical protein kinases (aPKC) that are critically involved in memory consolidation and maintenance. We examined the patterns of expression of two aPKC genes (Prkci and Prkcz) in rat cultured cortical neurons treated with histone deacetylase inhibitors. Histone hyperacetylation in the promoter region of Prkci gene elicited direct activation of transcriptional machinery, resulting in increased production of PKCλ mRNA. In parallel, histone hyperacetylation in the upstream promoter of Prkcz gene led to appearance of the corresponding PKCζ transcripts that are almost absent in the brain in resting conditions. In contrast, histone hyperacetylation in the downstream promoter of Prkcz gene was accompanied by a decreased expression of the brain-specific PKMζ products. We showed that epigenetically-triggered differential expression of PKMζ and PKCζ mRNA depended on protein synthesis. Summarizing, our results suggest that genes, encoding memory-related aPKC, may represent the molecular targets for epigenetic regulation through posttranslational histone modifications.

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References

Wang S, Sheng T, Ren S, Tian T, Lu W . Distinct Roles of PKCι/λ and PKMζ in the Initiation and Maintenance of Hippocampal Long-Term Potentiation and Memory. Cell Rep. 2016; 16(7):1954-61. DOI: 10.1016/j.celrep.2016.07.030. View

Federman N, Fustinana M, Romano A . Histone acetylation is recruited in consolidation as a molecular feature of stronger memories. Learn Mem. 2009; 16(10):600-6. DOI: 10.1101/lm.1537009. View

Borodinova A, Zuzina A, Balaban P . Role of Atypical Protein Kinases in Maintenance of Long-Term Memory and Synaptic Plasticity. Biochemistry (Mosc). 2017; 82(3):243-256. DOI: 10.1134/S0006297917030026. View

Elaut G, Torok G, Vinken M, Laus G, Papeleu P, Tourwe D . Major phase I biotransformation pathways of Trichostatin a in rat hepatocytes and in rat and human liver microsomes. Drug Metab Dispos. 2002; 30(12):1320-8. DOI: 10.1124/dmd.30.12.1320. View

Sacktor T . How does PKMζ maintain long-term memory?. Nat Rev Neurosci. 2010; 12(1):9-15. DOI: 10.1038/nrn2949. View

Hrabetova S, Sacktor T . Transient translocation of conventional protein kinase C isoforms and persistent downregulation of atypical protein kinase Mzeta in long-term depression. Brain Res Mol Brain Res. 2001; 95(1-2):146-52. DOI: 10.1016/s0169-328x(01)00185-1. View

Naik M, Benedikz E, Hernandez I, Libien J, Hrabe J, VALSAMIS M . Distribution of protein kinase Mzeta and the complete protein kinase C isoform family in rat brain. J Comp Neurol. 2000; 426(2):243-58. DOI: 10.1002/1096-9861(20001016)426:2<243::aid-cne6>3.0.co;2-8. View

Hsieh C, Tsokas P, Serrano P, Hernandez A, Tian D, Cottrell J . Persistent increased PKMζ in long-term and remote spatial memory. Neurobiol Learn Mem. 2016; 138:135-144. PMC: 5501180. DOI: 10.1016/j.nlm.2016.07.008. View

Bougie J, Lim T, Farah C, Manjunath V, Nagakura I, Ferraro G . The atypical protein kinase C in Aplysia can form a protein kinase M by cleavage. J Neurochem. 2009; 109(4):1129-43. PMC: 5154740. DOI: 10.1111/j.1471-4159.2009.06045.x. View

10.

Igaz L, Vianna M, Medina J, Izquierdo I . Two time periods of hippocampal mRNA synthesis are required for memory consolidation of fear-motivated learning. J Neurosci. 2002; 22(15):6781-9. PMC: 6758123. DOI: 20026642. View

11.

Connor S, Wang Y . A Place at the Table: LTD as a Mediator of Memory Genesis. Neuroscientist. 2015; 22(4):359-71. DOI: 10.1177/1073858415588498. View

12.

Shema R, Haramati S, Ron S, Hazvi S, Chen A, Sacktor T . Enhancement of consolidated long-term memory by overexpression of protein kinase Mzeta in the neocortex. Science. 2011; 331(6021):1207-10. DOI: 10.1126/science.1200215. View

13.

Bourtchouladze R, Abel T, Berman N, Gordon R, Lapidus K, Kandel E . Different training procedures recruit either one or two critical periods for contextual memory consolidation, each of which requires protein synthesis and PKA. Learn Mem. 1999; 5(4-5):365-74. PMC: 311273. View

14.

Wooten M, Zhou G, Wooten M, Seibenhener M . Transport of protein kinase C isoforms to the nucleus of PC12 cells by nerve growth factor: association of atypical zeta-PKC with the nuclear matrix. J Neurosci Res. 1997; 49(4):393-403. DOI: 10.1002/(sici)1097-4547(19970815)49:4<393::aid-jnr1>3.0.co;2-3. View

15.

Ranjan V, Singh S, Siddiqui S, Tripathi S, Khan M, Prakash A . Differential Histone Acetylation in Sub-Regions of Bed Nucleus of the Stria Terminalis Underlies Fear Consolidation and Extinction. Psychiatry Investig. 2017; 14(3):350-359. PMC: 5440438. DOI: 10.4306/pi.2017.14.3.350. View

16.

Hernandez A, Blace N, Crary J, Serrano P, Leitges M, Libien J . Protein kinase M zeta synthesis from a brain mRNA encoding an independent protein kinase C zeta catalytic domain. Implications for the molecular mechanism of memory. J Biol Chem. 2003; 278(41):40305-16. DOI: 10.1074/jbc.M307065200. View

17.

Siddiqui S, Singh S, Ranjan V, Ugale R, Saha S, Prakash A . Enhanced Histone Acetylation in the Infralimbic Prefrontal Cortex is Associated with Fear Extinction. Cell Mol Neurobiol. 2017; 37(7):1287-1301. PMC: 11482208. DOI: 10.1007/s10571-017-0464-6. View

18.

Serrano P, Yao Y, Sacktor T . Persistent phosphorylation by protein kinase Mzeta maintains late-phase long-term potentiation. J Neurosci. 2005; 25(8):1979-84. PMC: 6726070. DOI: 10.1523/JNEUROSCI.5132-04.2005. View

19.

Ling D, Benardo L, Sacktor T . Protein kinase Mzeta enhances excitatory synaptic transmission by increasing the number of active postsynaptic AMPA receptors. Hippocampus. 2006; 16(5):443-52. DOI: 10.1002/hipo.20171. View

20.

Lin Y, Flock K, Cook R, Hunkele A, Loh H, Ko J . Effects of trichostatin A on neuronal mu-opioid receptor gene expression. Brain Res. 2008; 1246:1-10. PMC: 2639711. DOI: 10.1016/j.brainres.2008.09.083. View