Chromatin and alternative splicing

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Alternative splicing affects more than 90% of human genes. Coupling between transcription and splicing has become crucial in the complex network underlying alternative splicing regulation. Because chromatin is the real template for nuclear transcription, changes in its structure, but also in the &qu...

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Detalles Bibliográficos
Autores principales:	Alló, M., Schor, I.E., Muñoz, M.J., De La Mata, M., Agirre, E., Valcárcel, J., Eyras, E., Kornblihtt, A.R.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2010
Materias:	double stranded RNA fibronectin messenger RNA mitogen activated protein kinase nerve cell adhesion molecule polypyrimidine tract binding protein RNA polymerase II small interfering RNA trichostatin A histone alternative RNA splicing article calcium signaling chromatin chromatin assembly and disassembly chromatin structure DNA fragmentation DNA methylation DNA replication DNA sequence exon gene mapping gene targeting genetic association genetic linkage heterochromatin histone acetylation human nerve cell differentiation nerve cell membrane steady potential nonhuman nucleosome posttranscriptional gene silencing priority journal promoter region RNA translation transcription regulation upregulation virus replication Article depolarization gene insertion gene silencing genome-wide association study histone modification medical literature molecular biology nerve cell stimulus Action Potentials Alternative Splicing Chromatin Chromatin Assembly and Disassembly DNA Replication Exons Histones Humans Models, Biological Neurons Nucleosomes
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00917451_v75_n_p103_Allo
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

Descripción
Sumario:	Alternative splicing affects more than 90% of human genes. Coupling between transcription and splicing has become crucial in the complex network underlying alternative splicing regulation. Because chromatin is the real template for nuclear transcription, changes in its structure, but also in the "reading" and "writing" of the histone code, could modulate splicing choices. Here, we discuss the evidence supporting these ideas, from the first proposal of chromatin affecting alternative splicing, performed 20 years ago, to the latest findings including genome-wide evidence that nucleosomes are preferentially positioned in exons. We focus on two recent reports from our laboratories that add new evidence to this field. The first report shows that a physiological stimulus such as neuron depolarization promotes intragenic histone acetylation (H3K9ac) and chromatin relaxation, causing the skipping of exon 18 of the neural cell adhesion molecule gene. In the second report, we show how specific histone modifications can be created at targeted gene regions as a way to affect alternative splicing: Using small interfering RNAs (siRNAs), we increased the levels of H3K9me2 and H3K27me3 in the proximity of alternative exon 33 of the human fibronectin gene, favoring its inclusion into mature messenger RNA (mRNA) through a mechanism that recalls RNAmediated transcriptional gene silencing. © 2010 Cold Spring Harbor Laboratory Press.

Chromatin and alternative splicing

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