Abstract
Activity-driven transcription is a key event associated with long-lasting forms of neuronal plasticity. Despite the efforts to investigate the regulatory mechanisms that control this complex process and the important advances in the knowledge of the function of many activity-induced genes in neurons, as well as the specific contribution of activity-regulated transcription factors, our understanding of how activity-driven transcription operates at the systems biology level is still very limited. This review focuses on the research of neuronal activity-driven transcription from an “omics” perspective. We will discuss the different high-throughput approaches undertaken to characterize the gene programs downstream of specific activity-regulated transcription factors, including CREB, SRF, MeCP2, Fos, Npas4, and others, and the interplay between epigenetic and transcriptional mechanisms underlying neuronal plasticity changes. Although basic questions remain unanswered and important challenges still lie ahead, the refinement of genome-wide techniques for investigating the neuronal transcriptome and epigenome promises great advances.
Similar content being viewed by others
References
Alberini CM (2009) Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 89(1):121–145
Saha RN, Dudek SM (2013) Splitting hares and tortoises: a classification of neuronal immediate early gene transcription based on poised RNA polymerase II. Neuroscience 247:175–181
Igaz LM, Vianna MR, Medina JH, Izquierdo I (2002) Two time periods of hippocampal mRNA synthesis are required for memory consolidation of fear-motivated learning. J Neurosci 22(15):6781–6789
Alberini CM (2008) The role of protein synthesis during the labile phases of memory: revisiting the skepticism. Neurobiol Learn Mem 89(3):234–246
Davis HP, Squire LR (1984) Protein synthesis and memory: a review. Psychol Bull 96(3):518–559
Seredenina T, Luthi-Carter R (2012) What have we learned from gene expression profiles in Huntington’s disease? Neurobiol Dis 45(1):83–98
Ferraiuolo L, Heath PR, Holden H, Kasher P, Kirby J, Shaw PJ (2007) Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. J Neurosci 27(34):9201–9219
Nagasaka Y, Dillner K, Ebise H, Teramoto R, Nakagawa H, Lilius L, Axelman K, Forsell C, Ito A, Winblad B, Kimura T, Graff C (2005) A unique gene expression signature discriminates familial Alzheimer’s disease mutation carriers from their wild-type siblings. Proc Natl Acad Sci U S A 102(41):14854–14859
Altar CA, Vawter MP, Ginsberg SD (2009) Target identification for CNS diseases by transcriptional profiling. Neuropsychopharmacology 34(1):18–54
Valor LM, Barco A (2010) Hippocampal gene profiling: toward a systems biology of the hippocampus. Hippocampus
Urdinguio RG, Sanchez-Mut JV, Esteller M (2009) Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol 8(11):1056–1072
Flavell SW, Greenberg ME (2008) Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system. Annu Rev Neurosci 31:563–590
Lu Y, Christian K, Lu B (2007) BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem
Cohen-Cory S, Kidane AH, Shirkey NJ, Marshak S (2010) Brain-derived neurotrophic factor and the development of structural neuronal connectivity. Dev Neurobiol 70(5):271–288
Bramham CR, Worley PF, Moore MJ, Guzowski JF (2008) The immediate early gene arc/arg3.1: regulation, mechanisms, and function. J Neurosci 28(46):11760–11767
Collingridge GL, Bliss TV (1995) Memories of NMDA receptors and LTP. Trends Neurosci 18(2):54–56
Loebrich S, Nedivi E (2009) The function of activity-regulated genes in the nervous system. Physiol Rev 89(4):1079–1103
Abraham WC, Williams JM (2008) LTP maintenance and its protein synthesis-dependence. Neurobiol Learn Mem 89(3):260–268
Zhang SJ, Steijaert MN, Lau D, Schutz G, Delucinge-Vivier C, Descombes P, Bading H (2007) Decoding NMDA receptor signaling: identification of genomic programs specifying neuronal survival and death. Neuron 53(4):549–562
Coba MP, Valor LM, Kopanitsa MV, Afinowi NO, Grant SG (2008) Kinase networks integrate profiles of N-methyl-D-aspartate receptor-mediated gene expression in hippocampus. J Biol Chem 283(49):34101–34107
Pegoraro S, Broccard FD, Ruaro ME, Bianchini D, Avossa D, Pastore G, Bisson G, Altafini C, Torre V (2010) Sequential steps underlying neuronal plasticity induced by a transient exposure to gabazine. J Cell Physiol 222(3):713–728
French PJ, O'Connor V, Voss K, Stean T, Hunt SP, Bliss TV (2001) Seizure-induced gene expression in area CA1 of the mouse hippocampus. Eur J Neurosci 14(12):2037–2041
Havik B, Rokke H, Dagyte G, Stavrum AK, Bramham CR, Steen VM (2007) Synaptic activity-induced global gene expression patterns in the dentate gyrus of adult behaving rats: induction of immunity-linked genes. Neuroscience 148(4):925–936
Ryan MM, Mason-Parker SE, Tate WP, Abraham WC, Williams JM (2010) Rapidly induced gene networks following induction of long-term potentiation at perforant path synapses in vivo. Hippocampus
Ploski JE, Park KW, Ping J, Monsey MS, Schafe GE (2010) Identification of plasticity-associated genes regulated by Pavlovian fear conditioning in the lateral amygdala. J Neurochem 112(3):636–650
Matsuo R, Kato A, Sakaki Y, Inokuchi K (1998) Cataloging altered gene expression during rat hippocampal long-term potentiation by means of differential display. Neurosci Lett 244(3):173–176
Wibrand K, Messaoudi E, Havik B, Steenslid V, Lovlie R, Steen VM, Bramham CR (2006) Identification of genes co-upregulated with Arc during BDNF-induced long-term potentiation in adult rat dentate gyrus in vivo. Eur J Neurosci 23(6):1501–1511
Altar CA, Laeng P, Jurata LW, Brockman JA, Lemire A, Bullard J, Bukhman YV, Young TA, Charles V, Palfreyman MG (2004) Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways. J Neurosci 24(11):2667–2677
Leil TA, Ossadtchi A, Cortes JS, Leahy RM, Smith DJ (2002) Finding new candidate genes for learning and memory. J Neurosci Res 68(2):127–137
Leil TA, Ossadtchi A, Nichols TE, Leahy RM, Smith DJ (2003) Genes regulated by learning in the hippocampus. J Neurosci Res 71(6):763–768
Cavallaro S, D'Agata V, Manickam P, Dufour F, Alkon DL (2002) Memory-specific temporal profiles of gene expression in the hippocampus. Proc Natl Acad Sci U S A 99(25):16279–16284
Levenson JM, Choi S, Lee SY, Cao YA, Ahn HJ, Worley KC, Pizzi M, Liou HC, Sweatt JD (2004) A bioinformatics analysis of memory consolidation reveals involvement of the transcription factor c-rel. J Neurosci 24(16):3933–3943
Hunsberger JG, Bennett AH, Selvanayagam E, Duman RS, Newton SS (2005) Gene profiling the response to kainic acid induced seizures. Brain Res Mol Brain Res 141(1):95–112
Hermey G, Mahlke C, Gutzmann JJ, Schreiber J, Bluthgen N, Kuhl D (2013) Genome-wide profiling of the activity-dependent hippocampal transcriptome. PLoS ONE 8(10):e76903
Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF (1993) Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron 11(2):371–386
Hevroni D, Rattner A, Bundman M, Lederfein D, Gabarah A, Mangelus M, Silverman MA, Kedar H, Naor C, Kornuc M, Hanoch T, Seger R, Theill LE, Nedivi E, Richter-Levin G, Citri Y (1998) Hippocampal plasticity involves extensive gene induction and multiple cellular mechanisms. J Mol Neurosci 10(2):75–98. doi:10.1007/BF02737120
Tang Y, Lu A, Aronow BJ, Wagner KR, Sharp FR (2002) Genomic responses of the brain to ischemic stroke, intracerebral haemorrhage, kainate seizures, hypoglycemia, and hypoxia. Eur J Neurosci 15(12):1937–1952
Lukasiuk K, Kontula L, Pitkanen A (2003) cDNA profiling of epileptogenesis in the rat brain. Eur J Neurosci 17(2):271–279
Newton SS, Collier EF, Hunsberger J, Adams D, Terwilliger R, Selvanayagam E, Duman RS (2003) Gene profile of electroconvulsive seizures: induction of neurotrophic and angiogenic factors. J Neurosci 23(34):10841–10851
Elliott RC, Miles MF, Lowenstein DH (2003) Overlapping microarray profiles of dentate gyrus gene expression during developmentand epilepsy-associated neurogenesis and axon outgrowth. J Neurosci 23(6):2218–2227
Lauren HB, Lopez-Picon FR, Brandt AM, Rios-Rojas CJ, Holopainen IE (2010) Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats. PLoS ONE 5(5):e10733. doi:10.1371/journal.pone.0010733
Peng H, Derrick BE, Martinez JL Jr (2003) Identification of upregulated SCG10 mRNA expression associated with late-phase longterm potentiation in the rat hippocampal Schaffer-CA1 pathway in vivo. J Neurosci 23(16):6617–6626
Lee PR, Cohen JE, Becker KG, Fields RD (2005) Gene expression in the conversion of early-phase to late-phase long-term potentiation. Ann N Y Acad Sci 1048:259–271
Xiang G, Pan L, Xing W, Zhang L, Huang L, Yu J, Zhang R, Wu J, Cheng J, Zhou Y (2007) Identification of activity-dependent gene expression profiles reveals specific subsets of genes induced by different routes of Ca(2+) entry in cultured rat cortical neurons. J Cell Physiol 212(1):126–136. doi:10.1002/jcp.21008
Kitamura C, Takahashi M, Kondoh Y, Tashiro H, Tashiro T (2007) Identification of synaptic activity-dependent genes by exposure of cultured cortical neurons to tetrodotoxin followed by its withdrawal. J Neurosci Res 85(11):2385–2399. doi:10.1002/jnr.21391
Thakker-Varia S, Alder J, Crozier RA, Plummer MR, Black IB (2001) Rab3A is required for brain-derived neurotrophic factorinduced synaptic plasticity: transcriptional analysis at the population and single-cell levels. J Neurosci 21(17):6782–6790
Alder J, Thakker-Varia S, Bangasser DA, Kuroiwa M, Plummer MR, Shors TJ, Black IB (2003) Brain-derived neurotrophic factorinduced gene expression reveals novel actions of VGF in hippocampal synaptic plasticity. J Neurosci 23(34):10800–10808
Ring RH, Alder J, Fennell M, Kouranova E, Black IB, Thakker-Varia S (2006) Transcriptional profiling of brain-derived-neurotrophic factor-induced neuronal plasticity: a novel role for nociceptin in hippocampal neurite outgrowth. J Neurobiol 66(4):361–377
Hayashi A, Kasahara T, Kametani M, Kato T (2008) Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking Xbp1. Biochem Biophys Res Commun 376(4):758–763. doi:10.1016/j.bbrc.2008.09.059
Cazzin C, Mion S, Caldara F, Rimland JM, Domenici E (2010) Microarray analysis of cultured rat hippocampal neurons treated with brain derived neurotrophic factor. Mol Biol Rep. doi:10.1007/s11033-010-0193-0
Luo Y, Long JM, Spangler EL, Longo DL, Ingram DK, Weng NP (2001) Identification of maze learning-associated genes in rat hippocampus by cDNA microarray. J Mol Neurosci 17(3):397–404. doi:10.1385/JMN:17:3:397
Ressler KJ, Paschall G, Zhou XL, Davis M (2002) Regulation of synaptic plasticity genes during consolidation of fear conditioning. J Neurosci 22(18):7892–7902
Donahue CP, Jensen RV, Ochiishi T, Eisenstein I, Zhao M, Shors T, Kosik KS (2002) Transcriptional profiling reveals regulated genes in the hippocampus during memory formation. Hippocampus 12(6):821–833
D'Agata V, Cavallaro S (2003) Hippocampal gene expression profiles in passive avoidance conditioning. Eur J Neurosci 18(10):2835–2841
Robles Y, Vivas-Mejia PE, Ortiz-Zuazaga HG, Felix J, Ramos X, Pena de Ortiz S (2003) Hippocampal gene expression profiling in spatial discrimination learning. Neurobiol Learn Mem 80(1):80–95
Mei B, Li C, Dong S, Jiang CH, Wang H, Hu Y (2005) Distinct gene expression profiles in hippocampus and amygdala after fear conditioning. Brain Res Bull 67(1–2):1–12. doi:10.1016/j.brainresbull.2005.03.023
McNair K, Broad J, Riedel G, Davies CH, Cobb SR (2007) Global changes in the hippocampal proteome following exposure to an enriched environment. Neuroscience 145(2):413–422
O'Sullivan NC, McGettigan PA, Sheridan GK, Pickering M, Conboy L, O'Connor JJ, Moynagh PN, Higgins DG, Regan CM, Murphy KJ (2007) Temporal change in gene expression in the rat dentate gyrus following passive avoidance learning. J Neurochem 101(4):1085–1098. doi:10.1111/j.1471-4159.2006.04418.x
Haberman RP, Lee HJ, Colantuoni C, Koh MT, Gallagher M (2008) Rapid encoding of new information alters the profile of plasticity-related mRNA transcripts in the hippocampal CA3 region. Proc Natl Acad Sci U S A 105(30):10601–10606. doi:10.1073/pnas.0804292105
Sirri A, Bianchi V, Pelizzola M, Mayhaus M, Ricciardi-Castagnoli P, Toniolo D, D'Adamo P (2010) Temporal gene expression profile of the hippocampus following trace fear conditioning. Brain Res 1308:14–23. doi:10.1016/j.brainres.2009.10.049
Li H, Gu X, Dawson VL, Dawson TM (2004) Identification of calcium- and nitric oxide-regulated genes by differential analysis of library expression (DAzLE). Proc Natl Acad Sci U S A 101(2):647–652
Hong SJ, Li H, Becker KG, Dawson VL, Dawson TM (2004) Identification and analysis of plasticity-induced late-response genes. Proc Natl Acad Sci U S A 101(7):2145–2150
Zhang SJ, Zou M, Lu L, Lau D, Ditzel DA, Delucinge-Vivier C, Aso Y, Descombes P, Bading H (2009) Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity. PLoS Genet 5(8):e1000604
Wang YY, Smith P, Murphy M, Cook M (2009) Global expression profiling in epileptogenesis: does it add to the confusion? Brain Pathol
Park CS, Gong R, Stuart J, Tang SJ (2006) Molecular network and chromosomal clustering of genes involved in synaptic plasticity in the hippocampus. J Biol Chem
Valor LM, Jancic D, Lujan R, Barco A (2010) Ultrastructural and transcriptional profiling of neuropathological misregulation of CREB function. Cell Death Differ 17(10):1636–1644
Mardis ER (2008) The impact of next-generation sequencing technology on genetics. Trends Genet 24(3):133–141
Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5(7):621–628
Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465(7295):182–187
Tanis KQ, Duman RS, Newton SS (2008) CREB binding and activity in brain: regional specificity and induction by electroconvulsive seizure. Biol Psychiatry 63(7):710–720
Saha RN, Wissink EM, Bailey ER, Zhao M, Fargo DC, Hwang JY, Daigle KR, Fenn JD, Adelman K, Dudek SM (2011) Rapid activity-induced transcription of Arc and other IEGs relies on poised RNA polymerase II. Nat Neurosci 14(7):848–856
West AE, Griffith EC, Greenberg ME (2002) Regulation of transcription factors by neuronal activity. Nat Rev Neurosci 3(12):921–931
Fass DM, Butler JE, Goodman RH (2003) Deacetylase activity is required for cAMP activation of a subset of CREB target genes. J Biol Chem 278(44):43014–43019. doi:10.1074/jbc.M305905200
Qi L, Saberi M, Zmuda E, Wang Y, Altarejos J, Zhang X, Dentin R, Hedrick S, Bandyopadhyay G, Hai T, Olefsky J, Montminy M (2009) Adipocyte CREB promotes insulin resistance in obesity. Cell Metab 9(3):277–286. doi:10.1016/j.cmet.2009.01.006
Euskirchen G, Royce TE, Bertone P, Martone R, Rinn JL, Nelson FK, Sayward F, Luscombe NM, Miller P, Gerstein M, Weissman S, Snyder M (2004) CREB binds to multiple loci on human chromosome 22. Mol Cell Biol 24(9):3804–3814
Koldamova R, Schug J, Lefterova M, Cronican AA, Fitz NF, Davenport FA, Carter A, Castranio EL, Lefterov I (2014) Genome-wide approaches reveal EGR1-controlled regulatory networks associated with neurodegeneration. Neurobiol Dis 63C:107–114
Matsuo K, Galson DL, Zhao C, Peng L, Laplace C, Wang KZ, Bachler MA, Amano H, Aburatani H, Ishikawa H, Wagner EF (2004) Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. J Biol Chem 279(25):26475–26480. doi:10.1074/jbc.M313973200
Lonze BE, Ginty DD (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35(4):605–623
Benito E, Barco A (2010) CREB’s control of intrinsic and synaptic plasticity: implications for CREB-dependent memory models. Trends Neurosci 33(5):230–240
Barco A, Marie H (2011) Genetic approaches to investigate the role of CREB in neuronal plasticity and memory. Mol Neurobiol 44(3):330–349
McClung CA, Nestler EJ (2003) Regulation of gene expression and cocaine reward by CREB and DeltaFosB. Nat Neurosci 6(11):1208–1215
Barco A, Patterson S, Alarcon JM, Gromova P, Mata-Roig M, Morozov A, Kandel ER (2005) Gene expression profiling of facilitated L-LTP in VP16-CREB mice reveals that BDNF is critical for the maintenance of LTP and its synaptic capture. Neuron 48(1):123–137
Benito E, Valor LM, Jimenez-Minchan M, Huber W, Barco A (2011) cAMP response element-binding protein is a primary hub of activity-driven neuronal gene expression. J Neurosci 31(50):18237–18250
Mayr B, Montminy M (2001) Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2(8):599–609
Hummler E, Cole TJ, Blendy JA, Ganss R, Aguzzi A, Schmid W, Beermann F, Schutz G (1994) Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. Proc Natl Acad Sci U S A 91(12):5647–5651
Blendy JA, Kaestner KH, Schmid W, Gass P, Schutz G (1996) Targeting of the CREB gene leads to up-regulation of a novel CREB mRNA isoform. EMBO J 15(5):1098–1106
Mantamadiotis T, Lemberger T, Bleckmann SC, Kern H, Kretz O, Martin Villalba A, Tronche F, Kellendonk C, Gau D, Kapfhammer J, Otto C, Schmid W, Schutz G (2002) Disruption of CREB function in brain leads to neurodegeneration. Nat Genet 31(1):47–54
Parlato R, Rieker C, Turiault M, Tronche F, Schutz G (2006) Survival of DA neurons is independent of CREM upregulation in absence of CREB. Genesis 44(10):454–464
Lemberger T, Parkitna JR, Chai M, Schutz G, Engblom D (2008) CREB has a context-dependent role in activity-regulated transcription and maintains neuronal cholesterol homeostasis. FASEB J 22(8):2872–2879
Jancic D, Lopez de Armentia M, Valor LM, Olivares R, Barco A (2009) Inhibition of cAMP response element-binding protein reduces neuronal excitability and plasticity, and triggers neurodegeneration. Cereb Cortex 19(11):2535–2547
Impey S, McCorkle SR, Cha-Molstad H, Dwyer JM, Yochum GS, Boss JM, McWeeney S, Dunn JJ, Mandel G, Goodman RH (2004) Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell 119(7):1041–1054
Conkright MD, Guzman E, Flechner L, Su AI, Hogenesch JB, Montminy M (2003) Genome-wide analysis of CREB target genes reveals a core promoter requirement for cAMP responsiveness. Mol Cell 11(4):1101–1108
Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, Chen H, Jenner R, Herbolsheimer E, Jacobsen E, Kadam S, Ecker JR, Emerson B, Hogenesch JB, Unterman T, Young RA, Montminy M (2005) Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci U S A 102(12):4459–4464
Lesiak A, Pelz C, Ando H, Zhu M, Davare M, Lambert TJ, Hansen KF, Obrietan K, Appleyard SM, Impey S, Wayman GA (2013) A genome-wide screen of CREB occupancy identifies the RhoA inhibitors Par6C and Rnd3 as regulators of BDNF-induced synaptogenesis. PLoS ONE 8(6):e64658
Treisman R (1987) Identification and purification of a polypeptide that binds to the c-fos serum response element. EMBO J 6(9):2711–2717
Sotiropoulos A, Gineitis D, Copeland J, Treisman R (1999) Signal-regulated activation of serum response factor is mediated by changes in actin dynamics. Cell 98(2):159–169
Sahai E, Alberts AS, Treisman R (1998) RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation. EMBO J 17(5):1350–1361
Knoll B (2010) Actin-mediated gene expression in neurons: the MRTF-SRF connection. Biol Chem 391(6):591–597
Knoll B, Nordheim A (2009) Functional versatility of transcription factors in the nervous system: the SRF paradigm. Trends Neurosci 32(8):432–442
Selvaraj A, Prywes R (2004) Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent. BMC Mol Biol 5:13
Philippar U, Schratt G, Dieterich C, Muller JM, Galgoczy P, Engel FB, Keating MT, Gertler F, Schule R, Vingron M, Nordheim A (2004) The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF. Mol Cell 16(6):867–880
Balza RO Jr, Misra RP (2006) Role of the serum response factor in regulating contractile apparatus gene expression and sarcomeric integrity in cardiomyocytes. J Biol Chem 281(10):6498–6510
Cooper SJ, Trinklein ND, Nguyen L, Myers RM (2007) Serum response factor binding sites differ in three human cell types. Genome Res 17(2):136–144
Sun K, Battle MA, Misra RP, Duncan SA (2009) Hepatocyte expression of serum response factor is essential for liver function, hepatocyte proliferation and survival, and postnatal body growth in mice. Hepatology 49(5):1645–1654
Stritt C, Stern S, Harting K, Manke T, Sinske D, Schwarz H, Vingron M, Nordheim A, Knoll B (2009) Paracrine control of oligodendrocyte differentiation by SRF-directed neuronal gene expression. Nat Neurosci 12(4):418–427
Ramanan N, Shen Y, Sarsfield S, Lemberger T, Schutz G, Linden DJ, Ginty DD (2005) SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability. Nat Neurosci 8(6):759–767
Etkin A, Alarcon JM, Weisberg SP, Touzani K, Huang YY, Nordheim A, Kandel ER (2006) A role in learning for SRF: deletion in the adult forebrain disrupts LTD and the formation of an immediate memory of a novel context. Neuron 50(1):127–143
Parkitna JR, Bilbao A, Rieker C, Engblom D, Piechota M, Nordheim A, Spanagel R, Schutz G (2010) Loss of the serum response factor in the dopamine system leads to hyperactivity. FASEB J 24(7):2427–2435
Stritt C, Knoll B (2010) Serum response factor regulates hippocampal lamination and dendrite development and is connected with reelin signaling. Mol Cell Biol 30(7):1828–1837
Stern S, Sinske D, Knoll B (2012) Serum response factor modulates neuron survival during peripheral axon injury. J Neuroinflammation 9:78
Sun Q, Chen G, Streb JW, Long X, Yang Y, Stoeckert CJ Jr, Miano JM (2006) Defining the mammalian CArGome. Genome Res 16(2):197–207
Zhang SX, Garcia-Gras E, Wycuff DR, Marriot SJ, Kadeer N, Yu W, Olson EN, Garry DJ, Parmacek MS, Schwartz RJ (2005) Identification of direct serum-response factor gene targets during Me2SO-induced P19 cardiac cell differentiation. J Biol Chem 280(19):19115–19126
Kaltschmidt B, Kaltschmidt C (2009) NF-kappaB in the nervous system. Cold Spring Harbor Perspect Biol 1(3):a001271
Guy J, Cheval H, Selfridge J, Bird A (2011) The role of MeCP2 in the brain. Annu Rev Cell Dev Biol 27:631–652
Flavell SW, Kim TK, Gray JM, Harmin DA, Hemberg M, Hong EJ, Markenscoff-Papadimitriou E, Bear DM, Greenberg ME (2008) Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection. Neuron 60(6):1022–1038
Rashid AJ, Cole CJ, Josselyn SA (2013) Emerging roles for MEF2 transcription factors in memory. Genes Brain Behav
McKinsey TA, Zhang CL, Olson EN (2002) MEF2: a calcium-dependent regulator of cell division, differentiation and death. Trends Biochem Sci 27(1):40–47
Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jeppesen P, Klein F, Bird A (1992) Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69(6):905–914
Meehan RR, Lewis JD, Bird AP (1992) Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucleic Acids Res 20(19):5085–5092
Skene PJ, Illingworth RS, Webb S, Kerr AR, James KD, Turner DJ, Andrews R, Bird AP (2010) Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell 37(4):457–468
Mellen M, Ayata P, Dewell S, Kriaucionis S, Heintz N (2012) MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 151(7):1417–1430
Tudor M, Akbarian S, Chen RZ, Jaenisch R (2002) Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain. Proc Natl Acad Sci U S A 99(24):15536–15541
Baker SA, Chen L, Wilkins AD, Yu P, Lichtarge O, Zoghbi HY (2013) An AT-hook domain in MeCP2 determines the clinical course of Rett syndrome and related disorders. Cell 152(5):984–996
Schoch H, Abel T (2014) Transcriptional co-repressors and memory storage. Neuropharmacology
Adachi M, Monteggia LM (2014) Decoding transcriptional repressor complexes in the adult central nervous system. Neuropharmacology
Flavell SW, Cowan CW, Kim TK, Greer PL, Lin Y, Paradis S, Griffith EC, Hu LS, Chen C, Greenberg ME (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311(5763):1008–1012
Wei W, Coelho CM, Li X, Marek R, Yan S, Anderson S, Meyers D, Mukherjee C, Sbardella G, Castellano S, Milite C, Rotili D, Mai A, Cole PA, Sah P, Kobor MS, Bredy TW (2012) p300/CBP-associated factor selectively regulates the extinction of conditioned fear. J Neurosci 32(35):11930–11941
Pulipparacharuvil S, Renthal W, Hale CF, Taniguchi M, Xiao G, Kumar A, Russo SJ, Sikder D, Dewey CM, Davis MM, Greengard P, Nairn AC, Nestler EJ, Cowan CW (2008) Cocaine regulates MEF2 to control synaptic and behavioral plasticity. Neuron 59(4):621–633
Nedivi E, Hevroni D, Naot D, Israeli D, Citri Y (1993) Numerous candidate plasticity-related genes revealed by differential cDNA cloning. Nature 363(6431):718–722
Qian Z, Gilbert ME, Colicos MA, Kandel ER, Kuhl D (1993) Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation. Nature 361(6411):453–457
Fleischmann A, Hvalby O, Jensen V, Strekalova T, Zacher C, Layer LE, Kvello A, Reschke M, Spanagel R, Sprengel R, Wagner EF, Gass P (2003) Impaired long-term memory and NR2A-type NMDA receptor-dependent synaptic plasticity in mice lacking c-Fos in the CNS. J Neurosci 23(27):9116–9122
Kaczmarek L, Siedlecki JA, Danysz W (1988) Proto-oncogene c-fos induction in rat hippocampus. Brain Res 427(2):183–186
Greenberg ME, Ziff EB, Greene LA (1986) Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. Science 234(4772):80–83
Morgan JI, Cohen DR, Hempstead JL, Curran T (1987) Mapping patterns of c-fos expression in the central nervous system after seizure. Science 237(4811):192–197
Kaczmarek L, Chaudhuri A (1997) Sensory regulation of immediate-early gene expression in mammalian visual cortex: implications for functional mapping and neural plasticity. Brain Res Brain Res Rev 23(3):237–256
Jalava A, Mai S (1994) Fos and Jun form cell specific protein complexes at the neuropeptide tyrosine promoter. Oncogene 9(8):2369–2375
Kuzniewska B, Rejmak E, Malik AR, Jaworski J, Kaczmarek L, Kalita K (2013) Brain-derived neurotrophic factor induces matrix metalloproteinase 9 expression in neurons via the serum response factor/c-Fos pathway. Mol Cell Biol 33(11):2149–2162
Ganguly K, Rejmak E, Mikosz M, Nikolaev E, Knapska E, Kaczmarek L (2013) Matrix metalloproteinase (MMP) 9 transcription in mouse brain induced by fear learning. J Biol Chem 288(29):20978–20991
Jaworski J, Biedermann IW, Lapinska J, Szklarczyk A, Figiel I, Konopka D, Nowicka D, Filipkowski RK, Hetman M, Kowalczyk A, Kaczmarek L (1999) Neuronal excitation-driven and AP-1-dependent activation of tissue inhibitor of metalloproteinases-1 gene expression in rodent hippocampus. J Biol Chem 274(40):28106–28112
Ziolkowska B, Przewlocka B, Mika J, Labuz D, Przewlocki R (1998) Evidence for Fos involvement in the regulation of proenkephalin and prodynorphin gene expression in the rat hippocampus. Brain Res Mol Brain Res 54(2):243–251
Herdegen T, Leah JD (1998) Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev 28(3):370–490
Cole CJ, Josselyn SA (2008) Transcription regulation of memory: CREB, CaMKIV, Fos/Jun, CBP, and SRF. In: Sweatt JD, Byrne JH (eds) Learning and memory: a comprehensive reference, vol 4. Elsevier, Oxford, pp 547–566
Kaczmarek L, Lapinska-Dzwonek J, Szymczak S (2002) Matrix metalloproteinases in the adult brain physiology: a link between c-Fos, AP-1 and remodeling of neuronal connections? EMBO J 21(24):6643–6648
Zhang J, Zhang D, McQuade JS, Behbehani M, Tsien JZ, Xu M (2002) c-fos regulates neuronal excitability and survival. Nat Genet 30(4):416–420
Wu Y, Zhang D, Lou D, Fan Y, Aronow B, Xu M, Zhang J (2004) C-fos regulates neuropeptide Y expression in mouse dentate gyrus. Neurosci Lett 363(1):6–10
Paletzki RF, Myakishev MV, Polesskaya O, Orosz A, Hyman SE, Vinson C (2008) Inhibiting activator protein-1 activity alters cocaine-induced gene expression and potentiates sensitization. Neuroscience 152(4):1040–1053
O'Donovan KJ, Tourtellotte WG, Millbrandt J, Baraban JM (1999) The EGR family of transcription-regulatory factors: progress at the interface of molecular and systems neuroscience. Trends Neurosci 22(4):167–173
Poirier R, Cheval H, Mailhes C, Garel S, Charnay P, Davis S, Laroche S (2008) Distinct functions of egr gene family members in cognitive processes. Front Neurosci 2(1):47–55
Svaren J, Ehrig T, Abdulkadir SA, Ehrengruber MU, Watson MA, Milbrandt J (2000) EGR1 target genes in prostate carcinoma cells identified by microarray analysis. J Biol Chem 275(49):38524–38531
Virolle T, Krones-Herzig A, Baron V, De Gregorio G, Adamson ED, Mercola D (2003) Egr1 promotes growth and survival of prostate cancer cells. Identification of novel Egr1 target genes. J Biol Chem 278(14):11802–11810
Arora S, Wang Y, Jia Z, Vardar-Sengul S, Munawar A, Doctor KS, Birrer M, McClelland M, Adamson E, Mercola D (2008) Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip. Genome Biol 9(11):R166
Fu M, Zhu X, Zhang J, Liang J, Lin Y, Zhao L, Ehrengruber MU, Chen YE (2003) Egr-1 target genes in human endothelial cells identified by microarray analysis. Gene 315:33–41
Kubosaki A, Tomaru Y, Tagami M, Arner E, Miura H, Suzuki T, Suzuki M, Suzuki H, Hayashizaki Y (2009) Genome-wide investigation of in vivo EGR-1 binding sites in monocytic differentiation. Genome Biol 10(4):R41
James AB, Conway AM, Morris BJ (2005) Genomic profiling of the neuronal target genes of the plasticity-related transcription factor—Zif268. J Neurochem 95(3):796–810
Baumgartel K, Tweedie-Cullen RY, Grossmann J, Gehrig P, Livingstone-Zatchej M, Mansuy IM (2009) Changes in the proteome after neuronal zif268 overexpression. J Proteome Res 8(7):3298–3316
Han S, Hong S, Mo J, Lee D, Choi E, Choi JS, Sun W, Lee HW, Kim H (2014) Impaired extinction of learned contextual fear memory in early growth response 1 knockout mice. Mol Cells 37(1):24–30
Lin Y, Bloodgood BL, Hauser JL, Lapan AD, Koon AC, Kim TK, Hu LS, Malik AN, Greenberg ME (2008) Activity-dependent regulation of inhibitory synapse development by Npas4. Nature 455(7217):1198–1204
Maya-Vetencourt JF (2013) Activity-dependent NPAS4 expression and the regulation of gene programs underlying plasticity in the central nervous system. Neural Plast 2013:683909
Ploski JE, Monsey MS, Nguyen T, DiLeone RJ, Schafe GE (2011) The neuronal PAS domain protein 4 (Npas4) is required for new and reactivated fear memories. PLoS ONE 6(8):e23760
Ramamoorthi K, Fropf R, Belfort GM, Fitzmaurice HL, McKinney RM, Neve RL, Otto T, Lin Y (2011) Npas4 regulates a transcriptional program in CA3 required for contextual memory formation. Science 334(6063):1669–1675
Bloodgood BL, Sharma N, Browne HA, Trepman AZ, Greenberg ME (2013) The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition. Nature 503(7474):121–125
Rudenko A, Dawlaty MM, Seo J, Cheng AW, Meng J, Le T, Faull KF, Jaenisch R, Tsai LH (2013) Tet1 is critical for neuronal activity-regulated gene expression and memory extinction. Neuron 79(6):1109–1122
Nerlov C (2007) The C/EBP family of transcription factors: a paradigm for interaction between gene expression and proliferation control. Trends Cell Biol 17(7):318–324
Hawk JD, Bookout AL, Poplawski SG, Bridi M, Rao AJ, Sulewski ME, Kroener BT, Manglesdorf DJ, Abel T (2012) NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors. J Clin Invest 122(10):3593–3602
McNulty SE, Barrett RM, Vogel-Ciernia A, Malvaez M, Hernandez N, Davatolhagh MF, Matheos DP, Schiffman A, Wood MA (2012) Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory. Learn Mem 19(12):588–592
Sweatt JD (2013) The emerging field of neuroepigenetics. Neuron 80(3):624–632
Rando OJ (2012) Combinatorial complexity in chromatin structure and function: revisiting the histone code. Curr Opin Genet Dev 22(2):148–155
Henikoff S, Shilatifard A (2011) Histone modification: cause or cog? Trends Genet 27(10):389–396
Turner BM (2012) The adjustable nucleosome: an epigenetic signaling module. Trends Genet 28(9):436–444
Gardner KE, Allis CD, Strahl BD (2011) Operating on chromatin, a colorful language where context matters. J Mol Biol 409(1):36–46
Lopez-Atalaya JP, Ito S, Valor LM, Benito E, Barco A (2013) Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition. Nucleic Acids Res 41(17):8072–8084
Kasper LH, Lerach S, Wang J, Wu S, Jeevan T, Brindle PK (2010) CBP/p300 double null cells reveal effect of coactivator level and diversity on CREB transactivation. EMBO J 29(21):3660–3672
Vecsey CG, Hawk JD, Lattal KM, Stein JM, Fabian SA, Attner MA, Cabrera SM, McDonough CB, Brindle PK, Abel T, Wood MA (2007) Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB: CBP-dependent transcriptional activation. J Neurosci 27(23):6128–6140
Valor LM, Pulopulos MM, Jimenez-Minchan M, Olivares R, Lutz B, Barco A (2011) Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation, but does not affect cell viability. J Neurosci 31(5):1652–1663
Crepaldi L, Policarpi C, Coatti A, Sherlock WT, Jongbloets BC, Down TA, Riccio A (2013) Binding of TFIIIC to sine elements controls the relocation of activity-dependent neuronal genes to transcription factories. PLoS Genet 9(8):e1003699
Maze I, Noh KM, Allis CD (2013) Histone regulation in the CNS: basic principles of epigenetic plasticity. Neuropsychopharmacology 38(1):3–22
Barr ML, Bertram EG (1951) The behaviour of nuclear structures during depletion and restoration of Nissl material in motor neurons. J Anat 85(2):171–181
Borden J, Manuelidis L (1988) Movement of the X chromosome in epilepsy. Science 242(4886):1687–1691
Billia F, Baskys A, Carlen PL, De Boni U (1992) Rearrangement of centromeric satellite DNA in hippocampal neurons exhibiting long-term potentiation. Brain Res Mol Brain Res 14(1–2):101–108
Wilczynski G (2014) Significance of higher-order nuclear architecture for neuronal function and dysfunction. Neuropharmacology
Walczak A, Szczepankiewicz AA, Ruszczycki B, Magalska A, Zamlynska K, Dzwonek J, Wilczek E, Zybura-Broda K, Rylski M, Malinowska M, Dabrowski M, Szczepinska T, Pawlowski K, Pyskaty M, Wlodarczyk J, Szczerbal I, Switonski M, Cremer M, Wilczynski GM (2013) Novel higher-order epigenetic regulation of the Bdnf gene upon seizures. J Neurosci 33(6):2507–2511
Geschwind DH, Konopka G (2009) Neuroscience in the era of functional genomics and systems biology. Nature 461(7266):908–915
Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5(2):101–113
Acknowledgments
Research at Barco’s lab is supported by the grants SAF2011-22855 from the Spanish Ministry of Science and Innovation and Prometeo/2012/005 from the Generalitat Valenciana.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Benito, E., Barco, A. The Neuronal Activity-Driven Transcriptome. Mol Neurobiol 51, 1071–1088 (2015). https://doi.org/10.1007/s12035-014-8772-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-014-8772-z