Rpd3/CoRest-mediated activity-dependent transcription regulates the flexibility in memory updating in Drosophila.
Mai Takakura, Reiko Nakagawa, Takeshi Ota, Yoko Kimura, Man Yung Ng, Abdalla G Alia, Hiroyuki Okuno, Yukinori Hirano
Author Information
Mai Takakura: Hakubi Center, Kyoto University Graduate School of Medicine, Konoecho, Yoshida, Sakyo-ku, Kyoto, Kyoto, 606-8315, Japan.
Reiko Nakagawa: Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, Kobe, 650-0047, Japan. ORCID
Takeshi Ota: Shionogi & Co., Ltd, Laboratory for Innovative Therapy Research, Drug Discovery Technologies 1, Shionogi Pharmaceutical Research Center, 3-1-1, Futaba-cho, Toyonaka-shi, Osaka, 561-0825, Japan.
Yoko Kimura: Hakubi Center, Kyoto University Graduate School of Medicine, Konoecho, Yoshida, Sakyo-ku, Kyoto, Kyoto, 606-8315, Japan.
Man Yung Ng: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Abdalla G Alia: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Hiroyuki Okuno: Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, 890-8544, Japan.
Yukinori Hirano: Hakubi Center, Kyoto University Graduate School of Medicine, Konoecho, Yoshida, Sakyo-ku, Kyoto, Kyoto, 606-8315, Japan. yukinori@ust.hk.
Consolidated memory can be preserved or updated depending on the environmental change. Although such conflicting regulation may happen during memory updating, the flexibility of memory updating may have already been determined in the initial memory consolidation process. Here, we explored the gating mechanism for activity-dependent transcription in memory consolidation, which is unexpectedly linked to the later memory updating in Drosophila. Through proteomic analysis, we discovered that the compositional change in the transcriptional repressor, which contains the histone deacetylase Rpd3 and CoRest, acts as the gating mechanism that opens and closes the time window for activity-dependent transcription. Opening the gate through the compositional change in Rpd3/CoRest is required for memory consolidation, but closing the gate through Rpd3/CoRest is significant to limit future memory updating. Our data indicate that the flexibility of memory updating is determined through the initial activity-dependent transcription, providing a mechanism involved in defining memory state.
References
Lionello-Denolf, K. M., McIlvane, W. J., Canovas, D. S., de Souza, D. G. & Barros, R. S. Reversal learning set and functional equivalence in children with and without autism. Psychol. Rec. 58, 15–36 (2008).
[PMID: 20186287]
D’Cruz, A. M. et al. Reduced behavioral flexibility in autism spectrum disorders. Neuropsychology 27, 152–160 (2013).
[PMID: 23527643]
Graff, J. et al. Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories. Cell 156, 261–276 (2014).
[PMID: 24439381]
Uematsu, A. et al. Modular organization of the brainstem noradrenaline system coordinates opposing learning states. Nat. Neurosci. 20, 1602–1611 (2017).
[PMID: 28920933]
Sun, W., Li, X. & An, L. Distinct roles of prelimbic and infralimbic proBDNF in extinction of conditioned fear. Neuropharmacology 131, 11–19 (2018).
[PMID: 29241651]
Yap, E. L. & Greenberg, M. E. Activity-regulated transcription: bridging the gap between neural activity and behavior. Neuron 100, 330–348 (2018).
[PMID: 30359600]
Alberini, C. M. & Kandel, E. R. The regulation of transcription in memory consolidation. Cold Spring Harb. Perspect. Biol. 7, a021741 (2014).
[PMID: 25475090]
Ebert, D. H. & Greenberg, M. E. Activity-dependent neuronal signalling and autism spectrum disorder. Nature 493, 327–337 (2013).
[PMID: 23325215]
Penney, J. & Tsai, L. H. Histone deacetylases in memory and cognition. Sci. Signal. 7, re12 (2014).
[PMID: 25492968]
Dash, P. K., Hochner, B. & Kandel, E. R. Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation. Nature 345, 718–721 (1990).
[PMID: 2141668]
Bourtchuladze, R. et al. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 59–68 (1994).
[PMID: 7923378]
Yin, J. C. et al. Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 79, 49–58 (1994).
[PMID: 7923376]
Alarcon, J. M. et al. Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 42, 947–959 (2004).
[PMID: 15207239]
Korzus, E., Rosenfeld, M. G. & Mayford, M. CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 42, 961–972 (2004).
[PMID: 15207240]
Gonzalez, G. A. & Montminy, M. R. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 59, 675–680 (1989).
[PMID: 2573431]
Sheng, M., Thompson, M. A. & Greenberg, M. E. CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science 252, 1427–1430 (1991).
[DOI: 10.1126/science.1646483]
Chrivia, J. C. et al. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365, 855–859 (1993).
[PMID: 8413673]
Awata, H. et al. The neural circuit linking mushroom body parallel circuits induces memory consolidation in Drosophila. Proc. Natl Acad. Sci. USA 116, 16080–16085 (2019).
[PMID: 31337675]
Greenberg, M. E., Ziff, E. B. & Greene, L. A. Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. Science 234, 80–83 (1986).
[PMID: 3749894]
Miyashita, T., Kikuchi, E., Horiuchi, J. & Saitoe, M. Long-term memory engram cells are established by c-Fos/CREB transcriptional cycling. Cell Rep. 25, 2716–2728 e2713 (2018).
[PMID: 30517860]
Yang, Y. et al. Chromatin remodeling inactivates activity genes and regulates neural coding. Science 353, 300–305 (2016).
[PMID: 27418512]
Guan, J. S. et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459, 55–60 (2009).
[PMID: 19424149]
Chen, W. G. et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302, 885–889 (2003).
[PMID: 14593183]
Sharma, N. et al. ARNT2 tunes activity-dependent gene expression through NCoR2-mediated repression and NPAS4-mediated activation. Neuron 102, 390–406 e399 (2019).
[PMID: 30846309]
Tully, T., Preat, T., Boynton, S. C. & Del Vecchio, M. Genetic dissection of consolidated memory in Drosophila. Cell 79, 35–47 (1994).
[PMID: 7923375]
McGuire, S. E., Deshazer, M. & Davis, R. L. Thirty years of olfactory learning and memory research in Drosophila melanogaster. Prog. Neurobiol. 76, 328–347 (2005).
[PMID: 16266778]
Cognigni, P., Felsenberg, J. & Waddell, S. Do the right thing: neural network mechanisms of memory formation, expression and update in Drosophila. Curr. Opin. Neurobiol. 49, 51–58 (2018).
[PMID: 29258011]
Aso, Y. et al. The neuronal architecture of the mushroom body provides a logic for associative learning. eLife 3, e04577 (2014).
[PMID: 25535793]
Hirano, Y. et al. Fasting launches CRTC to facilitate long-term memory formation in Drosophila. Science 339, 443–446 (2013).
[PMID: 23349290]
Chen, C. C. et al. Visualizing long-term memory formation in two neurons of the Drosophila brain. Science 335, 678–685 (2012).
[PMID: 22323813]
Wu, J. K. et al. Long-term memory requires sequential protein synthesis in three subsets of mushroom body output neurons in Drosophila. Sci. Rep. 7, 7112 (2017).
[PMID: 28769066]
Fitzsimons, H. L. & Scott, M. J. Genetic modulation of Rpd3 expression impairs long-term courtship memory in Drosophila. PLoS ONE 6, e29171 (2011).
[PMID: 22195015]
Mao, Z., Roman, G., Zong, L. & Davis, R. L. Pharmacogenetic rescue in time and space of the rutabaga memory impairment by using Gene-Switch. Proc. Natl Acad. Sci. USA 101, 198–203 (2004).
[PMID: 14684832]
Hamada, F. N. et al. An internal thermal sensor controlling temperature preference in Drosophila. Nature 454, 217–220 (2008).
[PMID: 18548007]
Honegger, K. S., Campbell, R. A. & Turner, G. C. Cellular-resolution population imaging reveals robust sparse coding in the Drosophila mushroom body. J. Neurosci. 31, 11772–11785 (2011).
[PMID: 21849538]
Turner, G. C., Bazhenov, M. & Laurent, G. Olfactory representations by Drosophila mushroom body neurons. J. Neurophysiol. 99, 734–746 (2008).
[PMID: 18094099]
Pagani, M. R., Oishi, K., Gelb, B. D. & Zhong, Y. The phosphatase SHP2 regulates the spacing effect for long-term memory induction. Cell 139, 186–198 (2009).
[PMID: 19804763]
Brunmeir, R., Lagger, S. & Seiser, C. Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation. Int. J. Dev. Biol. 53, 275–289 (2009).
[PMID: 19412887]
Klapoetke, N. C. et al. Independent optical excitation of distinct neural populations. Nat. Methods 11, 338–346 (2014).
[PMID: 24509633]
Kadosh, D. & Struhl, K. Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo. Genes Dev. 12, 797–805 (1998).
[PMID: 9512514]
Aggarwal, B. D. & Calvi, B. R. Chromatin regulates origin activity in Drosophila follicle cells. Nature 430, 372–376 (2004).
[PMID: 15254542]
Maeshima, K. et al. Nucleosomal arrays self-assemble into supramolecular globular structures lacking 30-nm fibers. EMBO J. 35, 1115–1132 (2016).
[PMID: 27072995]
Hirano, Y. et al. Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies. Nat. Commun. 7, 13471 (2016).
[PMID: 27841260]
Shuai, Y. et al. Forgetting is regulated through Rac activity in Drosophila. Cell 140, 579–589 (2010).
[PMID: 20178749]
Malik, A. N. et al. Genome-wide identification and characterization of functional neuronal activity-dependent enhancers. Nat. Neurosci. 17, 1330–1339 (2014).
[PMID: 25195102]
Jacob, P. F. & Waddell, S. Spaced training forms complementary long-term memories of opposite valence in Drosophila. Neuron 106, 977–991.e4 (2020).
Spiegel, I. et al. Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs. Cell 157, 1216–1229 (2014).
[PMID: 24855953]
Hrvatin, S. et al. Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat. Neurosci. 21, 120–129 (2018).
[PMID: 29230054]
Hu, S. C., Chrivia, J. & Ghosh, A. Regulation of CBP-mediated transcription by neuronal calcium signaling. Neuron 22, 799–808 (1999).
[PMID: 10230799]
Port, F., Chen, H. M., Lee, T. & Bullock, S. L. Optimized CRISPR/Cas tools for efficient germline and somatic genome engineering in Drosophila. Proc. Natl Acad. Sci. USA 111, E2967–E2976 (2014).
[PMID: 25002478]
Groth, A. C., Fish, M., Nusse, R. & Calos, M. P. Construction of transgenic Drosophila by using the site-specific integrase from phage phiC31. Genetics 166, 1775–1782 (2004).
[PMID: 15126397]
Dura, J. M., Preat, T. & Tully, T. Identification of linotte, a new gene affecting learning and memory in Drosophila melanogaster. J. Neurogenet. 9, 1–14 (1993).
[PMID: 8295074]
Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).
[PMID: 8223268]
Knop, M. et al. Epitope tagging of yeast genes using a PCR-based strategy: more tags and improved practical routines. Yeast 15, 963–972 (1999).
[PMID: 10407276]
Oertel-Buchheit, P., Reinbolt, J., John, M., Granger-Schnarr, M. & Schnarr, M. A LexA mutant repressor with a relaxed inter-domain linker. Protein Sci. 7, 512–515 (1998).
[PMID: 9521130]
Oya, E. et al. H3K14 ubiquitylation promotes H3K9 methylation for heterochromatin assembly. EMBO Rep. 20, e48111 (2019).
[PMID: 31468675]
Pino, L. K. et al. The Skyline ecosystem: informatics for quantitative mass spectrometry proteomics. Mass Spectrom. Rev. 39, 229–244 (2020).
[PMID: 28691345]
Dallman, J. E., Allopenna, J., Bassett, A., Travers, A. & Mandel, G. A conserved role but different partners for the transcriptional corepressor CoREST in fly and mammalian nervous system formation. J. Neurosci. 24, 7186–7193 (2004).
[PMID: 15306652]
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
[PMID: 24695404]
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
[PMID: 23104886]
Feng, J., Liu, T., Qin, B., Zhang, Y. & Liu, X. S. Identifying ChIP-seq enrichment using MACS. Nat. Protoc. 7, 1728–1740 (2012).
[PMID: 22936215]
Shen, L., Shao, N., Liu, X. & Nestler, E. ngs.plot: Quick mining and visualization of next-generation sequencing data by integrating genomic databases. BMC Genomics 15, 284 (2014).
[PMID: 24735413]
Liao, Y., Wang, J., Jaehnig, E. J., Shi, Z. & Zhang, B. WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 47, W199–W205 (2019).
[PMID: 31114916]
Anders, S., Pyl, P. T. & Huber, W. HTSeq––a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).
[PMID: 25260700]
Saldanha, A. J. Java Treeview–extensible visualization of microarray data. Bioinformatics 20, 3246–3248 (2004).
[PMID: 15180930]
Tully, T. & Quinn, W. G. Classical conditioning and retention in normal and mutant Drosophila melanogaster. J. Comp. Physiol. A 157, 263–277 (1985).
[PMID: 3939242]
Tamura, T. et al. Aging specifically impairs amnesiac-dependent memory in Drosophila. Neuron 40, 1003–1011 (2003).
[PMID: 14659098]
Perazzona, B., Isabel, G., Preat, T. & Davis, R. L. The role of cAMP response element-binding protein in Drosophila long-term memory. J. Neurosci. 24, 8823–8828 (2004).
[PMID: 15470148]
