INVESTIGADORES
MUÑOZ Manuel Javier
artículos
Título:
Chromatin and alternative splicing.
Autor/es:
ALLÓ M; SCHOR IE,; MUÑOZ MJ; DE LA MATA M; AGIRRE E; VALCÁRCEL J; EYRAS E; KORNBLIHTT AR.
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:
Abstract
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 RNA-mediated transcriptional gene silencing.