Artículo

Fiszbein, A.; Giono, L.E.; Quaglino, A.; Berardino, B.G.; Sigaut, L.; von Bilderling, C.; Schor, I.E.; Steinberg, J.H.E.; Rossi, M.; Pietrasanta, L.I.; Caramelo, J.J.; Srebrow, A.; Kornblihtt, A.R. "Alternative Splicing of G9a Regulates Neuronal Differentiation" (2016) Cell Reports. 14(12):2797-2808
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Abstract:

Chromatin modifications are critical for the establishment and maintenance of differentiation programs. G9a, the enzyme responsible for histone H3 lysine 9 dimethylation in mammalian euchromatin, exists as two isoforms with differential inclusion of exon 10 (E10) through alternative splicing. We find that the G9a methyltransferase is required for differentiation of the mouse neuronal cell line N2a and that E10 inclusion increases during neuronal differentiation of cultured cells, as well as in the developing mouse brain. Although E10 inclusion greatly stimulates overall H3K9me2 levels, it does not affect G9a catalytic activity. Instead, E10 increases G9a nuclear localization. We show that the G9a E10+ isoform is necessary for neuron differentiation and regulates the alternative splicing pattern of its own pre-mRNA, enhancing E10 inclusion. Overall, our findings indicate that by regulating its own alternative splicing, G9a promotes neuron differentiation and creates a positive feedback loop that reinforces cellular commitment to differentiation. Fiszbein et al. show that the histone methyltransferase G9a regulates alternative splicing of its own transcript, an event critical for neuron differentiation. Inclusion of exon 10 stimulates H3K9me2 levels and promotes nuclear localization of G9a, creating a positive feedback loop that reinforces the cellular commitment to differentiation. © 2016 The Authors.

Registro:

Documento: Artículo
Título:Alternative Splicing of G9a Regulates Neuronal Differentiation
Autor:Fiszbein, A.; Giono, L.E.; Quaglino, A.; Berardino, B.G.; Sigaut, L.; von Bilderling, C.; Schor, I.E.; Steinberg, J.H.E.; Rossi, M.; Pietrasanta, L.I.; Caramelo, J.J.; Srebrow, A.; Kornblihtt, A.R.
Filiación:Departamento de Fisiologia, Biologia Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET), Ciudad Universitaria Pabellón II, Buenos Aires, C1428EHA, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II, Buenos Aires, C1428EHA, Argentina
Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IFIBA-CONICET, Cuidad Universitaria Pabellón I, Buenos Aires, C1428EHA, Argentina
Instituto de Investigación en Biomedicina de Buenos Aires CONICET, Partner Institute of the Max Planck Society, Buenos Aires, C1425FQD, Argentina
Centro de Microscopías Avanzadas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Cuidad Universitaria, Buenos Aires, C1428EHA, Argentina
Fundación Instituto Leloir, Buenos Aires, C1405BWE, Argentina
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, 69117, Germany
Palabras clave:CRISPR associated protein; euchromatic histone lysine n methyltransferase 2; G9a protein; histone H3; histone methyltransferase; lysine methyltransferase 1C; messenger RNA; unclassified drug; azepine derivative; histone; histone lysine methyltransferase; isoprotein; n (1 benzyl 4 piperidinyl) 2 (hexahydro 4 methyl 1h 1,4 diazepin 1 yl) 6,7 dimethoxy 4 quinazolinamine; quinazoline derivative; retinoic acid; RNA precursor; small interfering RNA; alternative RNA splicing; amino acid sequence; amino terminal sequence; animal cell; animal experiment; Article; catalysis; chromatin immunoprecipitation; chromatin structure; controlled study; cytoplasm; enzyme activity; exon; feedback system; G9a gene; gene control; immunofluorescence; mouse; nonhuman; nuclear localization signal; phenotype; priority journal; promoter region; protein expression; protein function; protein localization; protein modification; signal transduction; upregulation; Western blotting; animal; antagonists and inhibitors; brain; C57BL mouse; cell differentiation; cell line; cell nucleus; cytology; drug effects; fluorescence microscopy; fluorescence resonance energy transfer; genetics; HeLa cell line; human; metabolism; methylation; nerve cell; real time polymerase chain reaction; reporter gene; RNA interference; Alternative Splicing; Animals; Azepines; Brain; Cell Differentiation; Cell Line; Cell Nucleus; Exons; Fluorescence Resonance Energy Transfer; Genes, Reporter; HeLa Cells; Histone-Lysine N-Methyltransferase; Histones; Humans; Methylation; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Neurons; Protein Isoforms; Quinazolines; Real-Time Polymerase Chain Reaction; RNA Interference; RNA Precursors; RNA, Small Interfering; Tretinoin
Año:2016
Volumen:14
Número:12
Página de inicio:2797
Página de fin:2808
DOI: http://dx.doi.org/10.1016/j.celrep.2016.02.063
Título revista:Cell Reports
Título revista abreviado:Cell Rep.
ISSN:22111247
CAS:histone, 9062-68-4; histone lysine methyltransferase, 9076-80-6; n (1 benzyl 4 piperidinyl) 2 (hexahydro 4 methyl 1h 1,4 diazepin 1 yl) 6,7 dimethoxy 4 quinazolinamine, 935693-62-2; retinoic acid, 302-79-4; Azepines; BIX 01294; Histone-Lysine N-Methyltransferase; Histones; Protein Isoforms; Quinazolines; RNA Precursors; RNA, Small Interfering; Tretinoin
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22111247_v14_n12_p2797_Fiszbein

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Citas:

---------- APA ----------
Fiszbein, A., Giono, L.E., Quaglino, A., Berardino, B.G., Sigaut, L., von Bilderling, C., Schor, I.E.,..., Kornblihtt, A.R. (2016) . Alternative Splicing of G9a Regulates Neuronal Differentiation. Cell Reports, 14(12), 2797-2808.
http://dx.doi.org/10.1016/j.celrep.2016.02.063
---------- CHICAGO ----------
Fiszbein, A., Giono, L.E., Quaglino, A., Berardino, B.G., Sigaut, L., von Bilderling, C., et al. "Alternative Splicing of G9a Regulates Neuronal Differentiation" . Cell Reports 14, no. 12 (2016) : 2797-2808.
http://dx.doi.org/10.1016/j.celrep.2016.02.063
---------- MLA ----------
Fiszbein, A., Giono, L.E., Quaglino, A., Berardino, B.G., Sigaut, L., von Bilderling, C., et al. "Alternative Splicing of G9a Regulates Neuronal Differentiation" . Cell Reports, vol. 14, no. 12, 2016, pp. 2797-2808.
http://dx.doi.org/10.1016/j.celrep.2016.02.063
---------- VANCOUVER ----------
Fiszbein, A., Giono, L.E., Quaglino, A., Berardino, B.G., Sigaut, L., von Bilderling, C., et al. Alternative Splicing of G9a Regulates Neuronal Differentiation. Cell Rep. 2016;14(12):2797-2808.
http://dx.doi.org/10.1016/j.celrep.2016.02.063