Artículo

Schor, I.E.; Rascovan, N.; Pelisch, F.; Alió, M.; Kornblihtt, A.R. "Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing" (2009) Proceedings of the National Academy of Sciences of the United States of America. 106(11):4325-4330
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

In search for physiological pathways affecting alternative splicing through its kinetic coupling with transcription, we found that membrane depolarization of neuronal cells triggers the skipping of exon 18 from the neural cell adhesion molecule (NCAM) mRNA, independently of the calcium/calmodulin protein kinase IV pathway. We show that this exon responds to RNA polymerase II elongation, because its inclusion is increased by a slow polymerase II mutant. Depolarization affects the chromatin template in a specific way, by causing H3K9 hyper-acetylation restricted to an internal region of the NCAM gene surrounding the alternative exon. This intragenic histone hyper-acetylation is not paralleled by acetylation at the promoter, is associated with chromatin relaxation, and is linked to H3K36 trimethylation. The effects on acetylation and splicing fully revert when the depolarizing conditions are withdrawn and can be both duplicated and potentiated by the histone deacetylase inhibitor trichostatin A. Our results are consistent with a mechanism involving the kinetic coupling of splicing and transcription in response to depolarization through intragenic epigenetic changes on a gene that is relevant for the differentiation and function of neuronal cells.

Registro:

Documento: Artículo
Título:Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing
Autor:Schor, I.E.; Rascovan, N.; Pelisch, F.; Alió, M.; Kornblihtt, A.R.
Filiación:Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Universidad de Buenos Aires, C1428EHA Buenos Aires, Argentina
Palabras clave:Histone acetylation; MRNA processing; Neuronal excitation; Transcription; calcium calmodulin dependent protein kinase; messenger RNA; nerve cell adhesion molecule; RNA polymerase II; trichostatin A; acetylation; alternative RNA splicing; animal cell; article; cell differentiation; cell elongation; cell function; cell membrane depolarization; chromatin; chromatin structure; controlled study; embryo; exon; gene location; genetic epigenesis; methylation; mutant; nerve cell; nonhuman; priority journal; promoter region; protein folding; rat; RNA splicing; transcription initiation; Acetylation; Alternative Splicing; Animals; Chromatin; Epigenesis, Genetic; Exons; Histones; Membrane Potentials; Neural Cell Adhesion Molecules; Neurons; Rats; RNA Polymerase II
Año:2009
Volumen:106
Número:11
Página de inicio:4325
Página de fin:4330
DOI: http://dx.doi.org/10.1073/pnas.0810666106
Título revista:Proceedings of the National Academy of Sciences of the United States of America
Título revista abreviado:Proc. Natl. Acad. Sci. U. S. A.
ISSN:00278424
CODEN:PNASA
CAS:calcium calmodulin dependent protein kinase, 97350-82-8; trichostatin A, 58880-19-6; Chromatin; Histones; Neural Cell Adhesion Molecules; RNA Polymerase II, 2.7.7.-
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v106_n11_p4325_Schor

Referencias:

  • Proudfoot, N.J., Integrating mRNA processing with transcription (2002) Cell, 108, pp. 501-512
  • Neugebauer, K.M., On the importance of being co-transcriptional (2002) J Cell Sci, 115, pp. 3865-3871
  • Bentley, D.L., Rules of engagement: Co-transcriptional recruitment of pre-mRNA processing factors (2005) Curr Opin Cell Biol, 17, pp. 251-256
  • Kornblihtt, A.R., Promoter usage and alternative splicing (2005) Curr Opin Cell Biol, 17, pp. 262-268
  • de la Mata, M., Kornblihtt, A.R., RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20 (2006) Nat Struct Mol Biol, 13, pp. 973-980
  • Millhouse, S., Manley, J.L., The C-terminal domain of RNA polymerase II functions as a phosphorylation-dependent splicing activator in a heterologous protein (2005) Mol Cell Biol, 25, pp. 533-544
  • Monsalve, M., Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1 (2000) Mol Cell, 6, pp. 307-316
  • Roberts, G.C., Co-transcriptional commitment to alternative splice site selection (1998) Nucleic Acids Res, 26, pp. 5568-5572
  • Eperon, L.P., Effects of RNA secondary structure on alternative splicing of pre-mRNA: Is folding limited to a region behind the transcribing RNA polymerase? (1988) Cell, 54, pp. 393-401
  • KadenerS, Antagonistic effects of T-Ag and VP16 reveal a role for RNA pol II elongation on alternative splicing (2001) EMBO J, 20, pp. 5759-5768
  • de la Mata, M., A slow RNA polymerase II affects alternative splicing in vivo (2003) Mol Cell, 12, pp. 525-532
  • Nogues, G., Influence of polymerase II processivity on alternative splicing depends on splice site strength (2003) J Biol Chem, 278, pp. 52166-52171
  • Cramer, P., Functional association between promoter structure and transcript alternative splicing (1997) Proc Natl Acad Sci USA, 94, pp. 11456-11460
  • Kornblihtt, A.R., Chromatin, transcript elongation and alternative splicing (2006) Nat Struct Mol Biol, 13, pp. 5-7
  • Sims III, R.J., Recognition of trimethylated histone H3 lysine 4facilitatesthe recruitment of transcription postinitiation factors and pre-mRNA splicing (2007) Mol Cell, 28, pp. 665-676
  • Batsche, E., The human SWI/SNF subunit Brm is a regulator of alternative splicing (2006) Nat Struct Mol Biol, 13, pp. 22-29
  • Lorincz, M.C., Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells (2004) Nat Struct Mol Biol, 11, pp. 1068-1075
  • Ule, J., Darnell, R.B., RNAbinding proteinsand the regulation of neuronal synaptic plasticity (2006) Curr Opin Neurobiol, 16, pp. 102-110
  • Li, Q., Neuronal regulation of alternative pre-mRNA splicing (2007) Nat Rev Neurosci, 8, pp. 819-831
  • Liu, S.J., Kaczmarek, L.K., The expression of two splice variants of the Kv3.1 potassium channel gene is regulated by different signaling pathways (1998) J Neurosci, 18, pp. 2881-2890
  • Rozic-Kotliroff, G., Zisapel, N., Ca2+ -dependent splicing of neurexin IIalpha (2007) Biochem Biophys Res Commun, 352, pp. 226-230
  • Xie, J., Black, D.L., A CaMK IV responsive RNA element mediates depolarization- induced alternative splicing of ion channels (2001) Nature, 410, pp. 936-939
  • An, P., Grabowski, P.J., Exon silencing by UAGG motifs in response to neuronal excitation (2007) PLoS Biol, 5, pp. e36
  • Lee, J.A., Depolarization and CaM kinase IV modulate NMDA receptor splicing through two essential RNA elements (2007) PLoS Biol, 5, pp. e40
  • Levenson, J.M., Sweatt, J.D., Epigenetic mechanisms in memory formation (2005) Nat Rev Neurosci, 6, pp. 108-118
  • Fischer, A., Recovery of learning and memory is associated with chromatin remodelling (2007) Nature, 447, pp. 178-182
  • Alarcon, J.M., Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: A model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration (2004) Neuron, 42, pp. 947-959
  • Guan, Z., Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure (2002) Cell, 111, pp. 483-493
  • Korzus, E., CBP histone acetyltransferase activityis a critical component of memory consolidation (2004) Neuron, 42, pp. 961-972
  • Chwang, W.B., The nuclear kinase mitogen-and stress-activated protein kinase 1 regulates hippocampal chromatin remodeling in memory for mation (2007) JNeurosci, 27, pp. 12732-12742
  • Levenson, J.M., Regulation of histone acetylation during memory formation in the hippocampus (2004) JBiol Chem, 279, pp. 40545-40559
  • Cunningham, B.A., Neural cell adhesion molecule: Structure, immunoglob-ulin-like domains, cell surface modulation, and alternative RNA splicing (1987) Science, 236, pp. 799-806
  • Pollerberg, G.E., Differentiation state-dependent surface mobilities of two forms of the neural cell adhesion molecule (1986) Nature, 324, pp. 462-465
  • Pollerberg, E.G., Selectiveexpression of the 180-kD component of the neural cell adhesion molecule N-CAM during development (1985) J Cell Biol, 101, pp. 1921-1929
  • Buttner, B., Cytoplasmic domain of NCAM 180 reduces NCAM-mediated neurite outgrowth (2004) J Neurosci Res, 75, pp. 854-860
  • Persohn, E., Immunohistological localization of the neural adhesion molecules L1 and N-CAM in the developing hippocampus of the mouse (1990) J Neurocytol, 19, pp. 807-819. , SchachnerM
  • Polo-Parada, L., Distinct roles of different neural cell adhesion molecule (NCAM) isoforms in synaptic maturation revealed by analysis of NCAM 180 kDa isoform-deficient mice (2004) J Neurosci, 24, pp. 1852-1864
  • Sytnyk, V., Neural cell adhesion molecule promotes accumulation of TGN organelles at sites of neuron-to-neuron contacts (2002) J Cell Biol, 159, pp. 649-661
  • Sytnyk, V., NCAM promotes assembly and activity-dependent remodeling of the postsynaptic signaling complex (2006) J Cell Biol, 174, pp. 1071-1085
  • Mayford, M., Modulation of an NCAM-related adhesion molecule with long-term synaptic plasticity in Aplysia (1992) Science, 256, pp. 638-644
  • Schacher, S., Cell-specific changes in expression of mRNAs encoding splice variants of Aplysia cell adhesion molecule accompany long-term synaptic plasticity (2000) J Neurobiol, 45, pp. 152-161
  • Hoffman, K.B., Delayed and isoform-specific effect of NMDA exposure on neural cell adhesion molecules in hippocampus (2001) Neurosci Res, 39, pp. 167-173
  • Tacke, R., Goridis, C., Alternative splicing in the neural cell adhesion molecule pre-mRNA: Regulation of exon 18 skipping depends on the 5'-splice site (1991) Genes Dev, 5, pp. 1416-1429
  • Huang, Y.S., CPEB3 and CPEB4 in neurons: Analysis of RNA-binding specificity and translational control of AMPA receptor GluR2 mRNA (2006) EMBO J, 25, pp. 4865-4876
  • Bannister, A.J., Spatial distribution of di-and tri-methyl lysine 36 of histone H3 at active genes (2005) J Biol Chem, 280, pp. 17732-17736
  • Krogan, N.J., Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II (2003) Mol Cell Biol, 23, pp. 4207-4218
  • Xiao, T., Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast (2003) Genes Dev, 17, pp. 654-663
  • Edmunds, J.W., Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation (2008) EMBO J, 27, pp. 406-420
  • Joshi, A.A., Struhl, K., Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to pol II elongation (2005) Mol Cell, 20, pp. 971-978
  • Keogh, M.C., Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex (2005) Cell, 123, pp. 593-605
  • Kunda, P., Evidence for the involvement of Tiam1 in axon formation (2001) J Neurosci, 21, pp. 2361-2372
  • Umlauf, D., Site-specific analysis of histone methylation and acetylation (2004) Methods Mol Biol, 287, pp. 99-120

Citas:

---------- APA ----------
Schor, I.E., Rascovan, N., Pelisch, F., Alió, M. & Kornblihtt, A.R. (2009) . Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proceedings of the National Academy of Sciences of the United States of America, 106(11), 4325-4330.
http://dx.doi.org/10.1073/pnas.0810666106
---------- CHICAGO ----------
Schor, I.E., Rascovan, N., Pelisch, F., Alió, M., Kornblihtt, A.R. "Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing" . Proceedings of the National Academy of Sciences of the United States of America 106, no. 11 (2009) : 4325-4330.
http://dx.doi.org/10.1073/pnas.0810666106
---------- MLA ----------
Schor, I.E., Rascovan, N., Pelisch, F., Alió, M., Kornblihtt, A.R. "Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing" . Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 11, 2009, pp. 4325-4330.
http://dx.doi.org/10.1073/pnas.0810666106
---------- VANCOUVER ----------
Schor, I.E., Rascovan, N., Pelisch, F., Alió, M., Kornblihtt, A.R. Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proc. Natl. Acad. Sci. U. S. A. 2009;106(11):4325-4330.
http://dx.doi.org/10.1073/pnas.0810666106