Alternative Splicing of G9a Regulates Neuronal Differentiation

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 fin...

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Autores principales:	Fiszbein, Ana, Giono, Luciana Eugenia, Quaglino, Ana, Sigaut, Lorena, von Bilderling, Catalina, Schor, Ignacio Esteban, Rossi, Mario, Srebrow, Anabella, Kornblihtt, Alberto Rodolfo
Publicado:	2016
Materias:	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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22111247_v14_n12_p2797_Fiszbein http://hdl.handle.net/20.500.12110/paper_22111247_v14_n12_p2797_Fiszbein
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_22111247_v14_n12_p2797_Fiszbein
record_format	dspace
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Fiszbein, Ana Giono, Luciana Eugenia Quaglino, Ana Sigaut, Lorena von Bilderling, Catalina Schor, Ignacio Esteban Rossi, Mario Srebrow, Anabella Kornblihtt, Alberto Rodolfo Alternative Splicing of G9a Regulates Neuronal Differentiation
topic_facet	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
description	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.
author	Fiszbein, Ana Giono, Luciana Eugenia Quaglino, Ana Sigaut, Lorena von Bilderling, Catalina Schor, Ignacio Esteban Rossi, Mario Srebrow, Anabella Kornblihtt, Alberto Rodolfo
author_facet	Fiszbein, Ana Giono, Luciana Eugenia Quaglino, Ana Sigaut, Lorena von Bilderling, Catalina Schor, Ignacio Esteban Rossi, Mario Srebrow, Anabella Kornblihtt, Alberto Rodolfo
author_sort	Fiszbein, Ana
title	Alternative Splicing of G9a Regulates Neuronal Differentiation
title_short	Alternative Splicing of G9a Regulates Neuronal Differentiation
title_full	Alternative Splicing of G9a Regulates Neuronal Differentiation
title_fullStr	Alternative Splicing of G9a Regulates Neuronal Differentiation
title_full_unstemmed	Alternative Splicing of G9a Regulates Neuronal Differentiation
title_sort	alternative splicing of g9a regulates neuronal differentiation
publishDate	2016
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22111247_v14_n12_p2797_Fiszbein http://hdl.handle.net/20.500.12110/paper_22111247_v14_n12_p2797_Fiszbein
work_keys_str_mv	AT fiszbeinana alternativesplicingofg9aregulatesneuronaldifferentiation AT gionolucianaeugenia alternativesplicingofg9aregulatesneuronaldifferentiation AT quaglinoana alternativesplicingofg9aregulatesneuronaldifferentiation AT sigautlorena alternativesplicingofg9aregulatesneuronaldifferentiation AT vonbilderlingcatalina alternativesplicingofg9aregulatesneuronaldifferentiation AT schorignacioesteban alternativesplicingofg9aregulatesneuronaldifferentiation AT rossimario alternativesplicingofg9aregulatesneuronaldifferentiation AT srebrowanabella alternativesplicingofg9aregulatesneuronaldifferentiation AT kornblihttalbertorodolfo alternativesplicingofg9aregulatesneuronaldifferentiation
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spelling	paper:paper_22111247_v14_n12_p2797_Fiszbein2023-06-08T16:35:12Z Alternative Splicing of G9a Regulates Neuronal Differentiation Fiszbein, Ana Giono, Luciana Eugenia Quaglino, Ana Sigaut, Lorena von Bilderling, Catalina Schor, Ignacio Esteban Rossi, Mario Srebrow, Anabella Kornblihtt, Alberto Rodolfo 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 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. Fil:Fiszbein, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Giono, L.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Quaglino, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Sigaut, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:von Bilderling, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Schor, I.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rossi, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Srebrow, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kornblihtt, A.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22111247_v14_n12_p2797_Fiszbein http://hdl.handle.net/20.500.12110/paper_22111247_v14_n12_p2797_Fiszbein

Alternative Splicing of G9a Regulates Neuronal Differentiation

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