INVESTIGADORES
KORNBLIHTT Alberto Rodolfo
artículos
Título:
Chromatin and alternative splicing
Autor/es:
ALLO, MARIANO; SCHOR, IGNACIO; MUÑOZ, MANUEL; DE LA MATA, MANUEL; AGIRRE, ENERITZ; VALCÁRCEL, JUAN; EYRAS, EDUARDO; KORNBLIHTT, ALBERTO R
Revista:
Cold Spring Harbor Symposia on Quantitative Biology
Editorial:
Cold Spring Harbor Laboratory Press
Referencias:
Año: 2010 vol. 75 p. 103 - 111
ISSN:
0091-7451
Resumen:
Alternative splicing affects more than 70% of human genes. Coupling between transcription and splicing has become crucial in the complex network underlying alternative splicing regulation. As 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, done 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 labs adding new evidence to this field. The first one 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 (NCAM) gene. In the second one, we show how specific histone modifications can be created at targeted gene regions as a way to affect alternative splicing: using small interference RNAs we increased the levels of H3K9me2 and H3K27me3 in the proximity of alternative exon 33 (E33, EDI or EDA) of the human fibronectin gene, favoring its inclusion into mature mRNA through a mechanism that recalls RNA-mediated transcriptional gene silencing.